SYNTHESIS AND BIOLOGICAL ACTIVITIES OF ACETAMINOPHEN AND IBUPROFEN METAL COMPLEXES OR DERIVATIVES: A REVIEW
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We reviewed scientific literature on the synthesis of acetaminophen and ibuprofen, as well as their derivatives and biological properties. The synthesis of acetaminophen involves the acetylation of 4-aminophenol and acetic anhydride, while ibuprofen is synthesised by reacting isobutyl benzene and acetic anhydride in four continuous reaction stages, which are Friedel-Crafts acylation, carbonyl reduction, chloride substitution, and Grignard reaction. To obtain their derivatives, modifications have been made either by complexing the main structure of the drug compound with metal elements or adding certain desired moieties, such as thiourea, amide, ammonium, halogen, silicon, and 1,3,4-oxadiazole. Ibuprofen and acetaminophen have been recognised as effective painkillers and anti-inflammatories. Recently, their derivatives have been implicated in a variety of biological effects. The biological activities of acetaminophen and ibuprofen derivatives have been reported to exhibit urease inhibition and inflammatory inhibition, as well as inhibit the proliferation of breast cancer cells MCF-7. Overall, this review article describes the synthesis of acetaminophen and ibuprofen derivatives, complete with their biological activities such as antimicrobial, antifungal, anti-inflammatory, urease inhibitors, and anticancer.
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Licensee MJS, Universiti Malaya, Malaysia. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
References
Ahmadi, A., Khalili, M., Olama, Z., Karami, S., & Nahri-Niknafs, B. (2017). Synthesis and Study of Analgesic and Anti-inflammatory Activities of Amide Derivatives of Ibuprofen. Mini-Reviews in Medicinal Chemistry, 17(9), 799–804. https://doi.org/10.2174/1389557516666161226155951
Ahmed, E. F., El-baky, R. M. A., Ahmed, A. B. F., Gameel, N., Aziz, N. A., Fadl, G., & Gad, M. (2016). Evaluation of antibacterial activity of some non- steroidal anti-inflammatory drugs against Escherichia coli causing urinary tract infection. African Journal of Microbiology Research, 10(34), 1408–1416. https://doi.org/10.5897/AJMR2016.8179
Ahn, K., Johnson, D. S., & Cravatt, B. F. (2009). Fatty acid amide hydrolase as a potential therapeutic target for the treatment of pain and CNS disorders. Expert Opinion on Drug Discovery, 4(7), 763–784. https://doi.org/10.1517/17460440903018857
Ahsan, M. J. (2018). Synthesis and cytotoxicity evaluation of [(2,4-dichlorophenoxy)methyl]-5-aryl-1,3,4-oxadiazole/4H-1,2,4-triazole analogues. Turkish Journal of Chemistry, 42(5), 1334–1343. https://doi.org/10.3906/kim-1803-25
Akhondzadeh, S. (2016). The importance of clinical trials in drug development. Avicenna Journal of Medical Biotechnology, 8(4), 2016.
Al-Amiery, A. A., Kadhum, A. A. H., & Mohamad, A. B. (2012). Antifungal and antioxidant activities of pyrrolidone thiosemicarbazone complexes. Bioinorganic Chemistry and Applications, 2012(L). https://doi.org/10.1155/2012/795812
Alghamdi, A., & Nazreen, S. (2020). Synthesis, characterization and cytotoxic study of 2-hydroxy benzothiazole incorporated 1,3,4-oxadiazole derivatives. Egyptian Journal of Chemistry, 63(2), 471–482. https://doi.org/10.21608/ejchem.2019.17265.2059
Ali Alderawy, M. Q., Raheem Alrubaie, L. A., & Sheri, F. H. (2020). Synthesis, characterization of ibuprofen n-acyl-1,3,4 oxadiazole derivatives and anticancer activity against MCF-7 cell line. Systematic Reviews in Pharmacy, 11(4), 681–689. https://doi.org/10.31838/srp.2020.4.100
Alkabodi, I., Almekhlafi, S., & Ibrahim, D. A. (2016). Synthesis and anti-inflammatory activity of novel aspirin and ibuprofen amide derivatives. Chemical and Pharmaceutical Research, 8(May 2019), 307–313.
AlKhalil, M., Al‐Hiari, Y., Kasabri, V., Arabiyat, S., Al‐Zweiri, M., Mamdooh, N., & Telfah, A. (2020). Selected pharmacotherapy agents as antiproliferative and anti‐inflammatory compounds. Drug Development Research, 81(4), 470–490. https://doi.org/10.1002/ddr.21640
Amin, R. R., Abo-elkassem, M., & Anwar, A. (2017). Synthesis , Characterization , and Spectroscopic Studies for New Cu ( II ), Co ( II ), Zn ( II ), Fe ( III ) And Zr ( II ) Complexes of Oxytetracycline Antibiotic , In vitro Antimicrobial Assessment Studies. Research and Reviews : Journal of Pharmacy and Pharmaceutical Sciences, 6(1), 38–48.
Amir, M., Akhter, M. W., & Alam, O. (2016). Synthesis, characterization, and biological evaluation of furoxan coupled ibuprofen derivatives as anti-inflammatory agents. Monatshefte Fur Chemie, 147(3), 493–508. https://doi.org/10.1007/s00706-015-1557-x
Annerberg, A., Lwin, K. M., Lindegardh, N., Khrutsawadchai, S., Ashley, E., Day, N. P. J. J., Singhasivanon, P., Tarning, J., White, N. J., & Nosten, F. (2011). A Small Amount of Fat Does Not Affect Piperaquine Exposure in Patients with Malaria ᰔ †. 55(9), 3971–3976. https://doi.org/10.1128/AAC.00279-11
Ansari, A., Ali, A., Asif, M., & Shamsuzzaman. (2017). Review: biologically active pyrazole derivatives. New Journal of Chemistry, 41(1), 16–41. https://doi.org/10.1039/C6NJ03181A
Antonenko, T. A., Gracheva, Y. A., Shpakovsky, D. B., Vorobyev, M. A., Tafeenko, V. A., Mazur, D. M., & Milaeva, E. R. (2022). Cytotoxic activity of organotin compounds containing non-steroidal anti-inflammatory drugs. Journal of Organometallic Chemistry, 960, 122191. https://doi.org/10.1016/j.jorganchem.2021.122191
Ashraf, Z., Mahmood, T., Hassan, M., Afzal, S., Rafique, H., Afzal, K., & Latip, J. (2019). Dexibuprofen amide derivatives as potential anticancer agents: Synthesis, in silico docking, bioevaluation, and molecular dynamic simulation. Drug Design, Development and Therapy, 13, 1643–1657. https://doi.org/10.2147/DDDT.S178595
Assefa, D. G., Zeleke, E. D., Bekele, D., Tesfahunei, H. A., Getachew, E., Joseph, M., & Manyazewal, T. (2021). Efficacy and safety of dihydroartemisinin – piperaquine versus artemether – lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Ugandan children : a systematic review and meta ‑ analysis of randomized control trials. Malaria Journal, 1–25. https://doi.org/10.1186/s12936-021-03711-4
Attia, M., Essa, E. A., Zaki, R. M., & Elkordy, A. A. (2020). An overview of the Antioxidant Effects of Ascorbic Acid and Alpha Lipoic Acid (In Liposomal Forms) as Adjuvant in Cancer Treatment. Antioxidants, 9(5), 1–15. https://doi.org/10.3390/antiox9050359
Ayipo, Y. O., Obaleye, J. A., & Badeggi, U. M. (2016). Novel metal complexes of mixed piperaquine-acetaminophen and piperaquine-acetylsalicylic acid: Synthesis, characterization and antimicrobial activities. Journal of the Turkish Chemical Society, Section A: Chemistry, 4(1), 313–313. https://doi.org/10.18596/jotcsa.287331
Ayipo, Y., Osunniran, W., Badeggi, U., Saheed, I., Jimoh, A., & Babamale, H. (2021). Synthesis, characterization and antibacterial study of Co(II) and Cu(II) complexes of mixed ligands of piperaquine and diclofenac. Journal of the Turkish Chemical Society Section A: Chemistry, 8(2), 633–650. https://doi.org/10.18596/jotcsa.898523
Babamale, H., Lawal, A., Rajee, O., & Oloyede, E. (2016). Synthesis , Characterization and Biological Activity Studies of Mixed Paracetamol- Ascorbic Acid Metal Complexes . Applied Science Environment, 20(4), 1157–1161. https://doi.org/http://dx.doi.org/10.4314/jasem.v20i4.32
Badea, G. I., & Radu, G. L. (2018). Introductory Chapter: Carboxylic Acids - Key Role in Life Sciences. In Carboxylic Acid - Key Role in Life Sciences (pp. 1–6). InTech. https://doi.org/10.5772/intechopen.77021
Bamigboye, M. O., Ejidike, I. P., & Ahmed, R. N. (2019). Antibacterial activities of Some Mixed Isoniazid-Ibuprofen Metal Complexes : Chelation and Characterization. Natural & Applied Science Journal, 2(2). https://doi.org/10.38061/idunas.631229
Barba, F. J., Esteve, M. J., & Frígola, A. (2014). Chapter 11 - Bioactive Components from Leaf Vegetable Products. In B. T.-S. in N. P. C. Atta-ur-Rahman (Ed.), Studies in Natural Products Chemistry (Vol. 41, pp. 321–346). Elsevier. https://doi.org/https://doi.org/10.1016/B978-0-444-63294-4.00011-5
Bateman, D. N., Carroll, R., Pettie, J., Yamamoto, T., Elamin, M. E. M. O., Peart, L., Dow, M., Coyle, J., Cranfield, K. R., Hook, C., Sandilands, E. A., Veiraiah, A., Webb, D., Gray, A., Dargan, P. I., Wood, D. M., Thomas, S. H. L., Dear, J. W., & Eddleston, M. (2014). Effect of the UK’s revised paracetamol poisoning management guidelines on admissions, adverse reactions and costs of treatment. British Journal of Clinical Pharmacology, 78(3), 610–618. https://doi.org/10.1111/bcp.12362
Bhandari, S. V., Bothara, K. G., Raut, M. K., Patil, A. A., Sarkate, A. P., & Mokale, V. J. (2008). Design, Synthesis and Evaluation of Antiinflammatory, Analgesic and Ulcerogenicity studies of Novel S-Substituted phenacyl-1,3,4-oxadiazole-2-thiol and Schiff bases of Diclofenac acid as Nonulcerogenic Derivatives. Bioorganic and Medicinal Chemistry, 16(4), 1822–1831. https://doi.org/10.1016/j.bmc.2007.11.014
Biotechnology, N. C. for. (n.d.). Prednisolone. PubChem Compound. https://doi.org/CID 5755
Bonakdar, A. P. S., Vafaei, F., Farokhpour, M., Esfahani, M. H. N., & Massah, A. R. (2017). Synthesis and anticancer activity assay of novel chalcone-sulfonamide derivatives. Iranian Journal of Pharmaceutical Research, 16(2), 565–568.
Caparrotta, T. M., Antoine, D. J., & Dear, J. W. (2018). Are some people at increased risk of paracetamol-induced liver injury? A critical review of the literature. European Journal of Clinical Pharmacology, 74(2), 147–160. https://doi.org/10.1007/s00228-017-2356-6
Chawla, G., Naaz, B., & Siddiqui, A. A. (2018). Exploring 1,3,4-Oxadiazole Scaffold for Anti-inflammatory and Analgesic Activities: A Review of Literature From 2005-2016. Mini-Reviews in Medicinal Chemistry, 18(3), 216–233. https://doi.org/10.2174/1389557517666170127121215
Chudobova, D., Dostalova, S., Ruttkay-Nedecky, B., Guran, R., Rodrigo, M. A. M., Tmejova, K., Krizkova, S., Zitka, O., Adam, V., & Kizek, R. (2015). The effect of metal ions on Staphylococcus aureus revealed by biochemical and mass spectrometric analyses. Microbiological Research, 170(June 2014), 147–156. https://doi.org/10.1016/j.micres.2014.08.003
Collignon, P. C., Conly, J. M., Andremont, A., McEwen, S. A., & Aidara-Kane, A. (2016). World Health Organization Ranking of Antimicrobials According to Their Importance in Human Medicine: A Critical Step for Developing Risk Management Strategies to Control Antimicrobial Resistance From Food Animal Production. Clinical Infectious Diseases, 63(8), 1087–1093. https://doi.org/10.1093/cid/ciw475
Colunga Biancatelli, R. M. L., Berrill, M., & Marik, P. E. (2020). The antiviral properties of vitamin C. Expert Review of Anti-Infective Therapy, 18(2), 99–101. https://doi.org/10.1080/14787210.2020.1706483
Cong, W., Sun, Y., Sun, Y. F., Yan, W. Bin, Zhang, Y. L., Gao, Z. F., Wang, C. H., Hou, G. G., & Zhang, J. J. (2021). Trifluoromethyl-substituted 3,5-bis(arylidene)-4-piperidones as potential anti-hepatoma and anti-inflammation agents by inhibiting NF-кB activation. Journal of Enzyme Inhibition and Medicinal Chemistry, 36(1), 1622–1631. https://doi.org/10.1080/14756366.2021.1953996
Dainese, enrico, Oddi, S., Simonetti, M., Sabatucci, A., Angelucci, clotilde B., Ballone, A., Dufrusine, B., Fezza, F., De fabritiis, G., Maccarrone, M., Dainese, enrico, & Oddi, S. (2020). the endocannabinoid hydrolase fAAH is an allosteric enzyme. Scientific Report:Naturereserach, 10(2292). https://doi.org/10.1038/s41598-020-59120-1
Damilola, A., Olagboye, S. A., & Akinwunmi, O. . (2019). Antimicrobial Activities of Novel Synthesized Cu(II) and Co(II) Mixed Ligand Complexes of Prednisolone and Paracetamol. International Journal of Scientific & Engineering Researc, 10(September). https://doi.org/10.13140/RG.2.2.10396.72323
Deplano, A., Cipriano, M., Moraca, F., Novellino, E., Catalanotti, B., Fowler, C. J., & Onnis, V. (2019). Benzylamides and piperazinoarylamides of ibuprofen as fatty acid amide hydrolase inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry, 34(1), 562–576. https://doi.org/10.1080/14756366.2018.1532418
Deplano, A., Karlsson, J., Svensson, M., Moraca, F., Catalanotti, B., Fowler, C. J., & Onnis, V. (2020). Exploring the fatty acid amide hydrolase and cyclooxygenase inhibitory properties of novel amide derivatives of ibuprofen. Journal of Enzyme Inhibition and Medicinal Chemistry, 35(1), 815–823. https://doi.org/10.1080/14756366.2020.1743283
Dinarello, C. A. (2010). Anti-inflammatory Agents: Present and Future. Cell, 140(6), 935–950. https://doi.org/10.1016/j.cell.2010.02.043
El-Sayed, S., Metwally, K., El-Shanawani, A. A., Abdel-Aziz, L. M., Pratsinis, H., & Kletsas, D. (2017). Synthesis and anticancer activity of novel quinazolinone-based rhodanines. Chemistry Central Journal, 11(1), 1–10. https://doi.org/10.1186/s13065-017-0333-x
Ennis, Z. N., Dideriksen, D., Vægter, H. B., Handberg, G., & Pottegård, A. (2016). Acetaminophen for Chronic Pain: A Systematic Review on Efficacy. Basic and Clinical Pharmacology and Toxicology, 118(3), 184–189. https://doi.org/10.1111/bcpt.12527
Fang, W. Y., Ravindar, L., Rakesh, K. P., Manukumar, H. M., Shantharam, C. S., Alharbi, N. S., & Qin, H. L. (2019). Synthetic approaches and pharmaceutical applications of chloro-containing molecules for drug discovery: A critical review. European Journal of Medicinal Chemistry, 173, 117–153. https://doi.org/10.1016/j.ejmech.2019.03.063
Fejzagić, A. V., Gebauer, J., Huwa, N., & Classen, T. (2019). Halogenating enzymes for active agent synthesis: First steps are done and many have to follow. Molecules, 24(21). https://doi.org/10.3390/molecules24214008
Garza-Cervantes, J. A., Chávez-Reyes, A., Castillo, E. C., García-Rivas, G., Ortega-Rivera, O. A., Salinas, E., Ortiz-Martínez, M., Gómez-Flores, S. L., Peña-Martínez, J. A., Pepi-Molina, A., Treviño-González, M. T., Zarate, X., Cantú-Cárdenas, M. E., Escarcega-Gonzalez, C. E., & Morones-Ramírez, J. R. (2017). Synergistic antimicrobial effects of silver/transition-metal combinatorial treatments. Scientific Reports, 7(1), 1–16. https://doi.org/10.1038/s41598-017-01017-7
Gerriets, V., Anderson, J., & Nappe, T. M. (2021). Acetaminophen. 1–5.
Ghani, H., & Yousif, E. (2021). Chemistry of Some Organotin Compounds. Al-Nahrain Journal of Science, 24(3), 9–15. https://doi.org/10.22401/ANJS.24.3.02
Glomb, T., & Świątek, P. (2021). Antimicrobial Activity of 1,3,4-Oxadiazole Derivatives. International Journal of Molecular Sciences, 22(13), 6979. https://doi.org/10.3390/ijms22136979
Glomb, T., Szymankiewicz, K., & Świątek, P. (2018). Anti-Cancer Activity of Derivatives of 1,3,4-Oxadiazole. Molecules, 23(12), 3361. https://doi.org/10.3390/molecules23123361
Golonka, I., Oleksy, M., Junka, A., Matera-witkiewicz, A., Bartoszewicz, M., & Musiał, W. (2017). Selected Physicochemical and Biological Properties of Ethyl Ascorbic Acid Compared to Ascorbic Acid. Biol. Pharm. Bull., 40(8), 1199–1206. https://doi.org/10.1248/bpb.b16-00967
Gomaa, S. (2018). Adverse effects induced by diclofenac , ibuprofen , and paracetamol toxicity on immunological and biochemical parameters in Swiss albino mice. Basic and Applied Zoology, 79(5), 1–9. https://doi.org/10.1186/s41936-018-0025-7
Goodman, M. C., Xu, S., Rouzer, C. A., Banerjee, S., Ghebreselasie, K., Migliore, M., Piomelli, D., & Marnett, L. J. (2018). Dual cyclooxygenase–fatty acid amide hydrolase inhibitor exploits novel binding interactions in the cyclooxygenase active site. Journal of Biological Chemistry, 293(9), 3028–3038. https://doi.org/10.1074/jbc.M117.802058
Haider, S., Alam, M. S., Hamid, H., Umar, S., Kumar, D., & Nazreen, S. (2018). Synthesis of novel amide containing Schiffs bases of 5-(4-chloro-phenyl)-furan-2-carboxaldehyde: Their in vivo anti-inflammatory, antioxidant and antinociceptive activities with ulcerogenic risk evaluation. Journal of Reports in Pharmaceutical Sciences, 7(1), 44–63.
Hassanzadeh, F., Jafari, E., Zarabi, M., Khodarahmi, G., & Vaseghi, G. (2020). Synthesis , cytotoxic evaluation , and molecular docking studies of some. 15(October), 454–462. https://doi.org/10.4103/1735-5362.297848
Hazra, S., Paul, A., Sharma, G., Koch, B., da Silva, M. F. C. G., & Pombeiro, A. J. L. (2016). Sulfonated Schiff base Sn(IV) complexes as potential anticancer agents. Journal of Inorganic Biochemistry, 162, 83–95. https://doi.org/10.1016/j.jinorgbio.2016.06.008
He, X., Nie, Y., Zhong, M., Li, S., Li, X., Guo, Y., Liu, Z., Gao, Y., Ding, F., Wen, D., & Zhang, Y. (2021). New organoselenides (NSAIDs-Se derivatives) as potential anticancer agents: Synthesis, biological evaluation and in silico calculations. European Journal of Medicinal Chemistry, 218, 113384. https://doi.org/10.1016/j.ejmech.2021.113384
Hegde, P., Boshoff, H. I. M., Rusman, Y., Wedajo, W., Salomon, C. E., Dick, T., & Aldrich, C. C. (2021). Reinvestigation of the structure-activity relationships of isoniazid. Tuberculosis, 129(March), 102100. https://doi.org/10.1016/j.tube.2021.102100
Hernandez-Patlan, D., B.Solis-Cruz, Mendez-Albores, A., Latorre, Hernandez-Velasco, J. D., X., R., L.-A., & Tellez, G. (2017). Comparison of PrestoBlue â and plating method to evaluate antimicrobial activity of ascorbic acid , boric acid and curcumin in an in vitro gastrointestinal model. Applied Microbiology, 124(2), 423–430. https://doi.org/10.1111/jam.13659
Hill, R. G., & Rang, H. P. (2013). Drug Discovery & Development - Technology in Transition (R. G. Hill & H. P. Rang (eds.); 2nd ed.). Churchill Livingstone, ELSEVIER.
Hu, Y., Zhang, S., Zhao, F., Gao, C., Feng, L., Lv, Z., Xu, Z., & Wu, X. (2017). SC. European Journal of Medicinal Chemistry. https://doi.org/10.1016/j.ejmech.2017.04.002
Hughes, J. P., Rees, S., Kalindjian, S. B., Philpott, K. L., Philpott, K., & Building, H. (2011). Principles of early drug discovery Correspondence. https://doi.org/10.1111/j.1476-5381.2010.01127.x
Ibuprofen Synthesis – Writing Anthology. (n.d.). Retrieved March 22, 2021, from https://central.edu/writing-anthology/2019/04/11/ibuprofen-synthesis/
Iqbal Farooqi, S., Arshad, N., Perveen, F., Ali Channar, P., Saeed, A., Javed, A., Hökelek, T., & Flörke, U. (2020). Structure and surface analysis of ibuprofen-organotin conjugate: Potential anti-cancer drug candidacy of the compound is proven by in-vitro DNA binding and cytotoxicity studies. Polyhedron, 192, 114845. https://doi.org/10.1016/j.poly.2020.114845
Iseh, A. L., Adegbola, A. J., & Adeagbo, B. A. (2017). Pharmacokinetic Characterization of Piperaquine in Nigerian Healthy Volunteers after Co-administration with a Commercial Brand of Moringa Tea. 15(January 2016), 1–10. https://doi.org/10.9734/BJPR/2017/32723
Kafarski, P., & Talma, M. (2018). Recent advances in design of new urease inhibitors: A review. Journal of Advanced Research, 13, 101–112. https://doi.org/10.1016/j.jare.2018.01.007
Kanwal, F. S., Khan, K. M., Khan, A., Ali, M., & Khalil, R. (2021). Biology ‑ oriented drug synthesis ( BIODS ), in vitro urease inhibitory activity , and in silico studies on ibuprofen derivatives. Molecular Diversity, 25(1), 143–157. https://doi.org/10.1007/s11030-019-10032-x
Khanam, R., Ahmad, K., Hejazi, I. I., Siddique, I. A., Kumar, V., Bhat, A. R., Azam, A., & Athar, F. (2017). Inhibitory growth evaluation and apoptosis induction in MCF-7 cancer cells by new 5-aryl-2-butylthio-1,3,4-oxadiazole derivatives. Cancer Chemotherapy and Pharmacology, 80(5), 1027–1042. https://doi.org/10.1007/s00280-017-3414-6
Kiriiri, G. K., Njogu, P. M., & Mwangi, A. N. (2020). Exploring different approaches to improve the success of drug discovery and development projects: a review. Future Journal of Pharmaceutical Sciences, 6(1). https://doi.org/10.1186/s43094-020-00047-9
Kleemiss, F., Justies, A., Duvinage, D., Watermann, P., Ehrke, E., Sugimoto, K., Fugel, M., Malaspina, L. A., Dittmer, A., Kleemiss, T., Puylaert, P., King, N. R., Staubitz, A., Tzschentke, T. M., Dringen, R., Grabowsky, S., & Beckmann, J. (2020). Sila-Ibuprofen. Journal of Medicinal Chemistry, 63(21), 12614–12622. https://doi.org/10.1021/acs.jmedchem.0c00813
Kumari, R., Banerjee, S., Roy, P., & Nath, M. (2020). Organotin(IV) complexes of NSAID, ibuprofen, X-ray structure of Ph3Sn(IBF), binding and cleavage interaction with DNA and in vitro cytotoxic studies of several organotin complexes of drugs. Applied Organometallic Chemistry, 34(1), 1–24. https://doi.org/10.1002/aoc.5283
Kumawat, A., Raheem, S., Ali, F., Dar, T. A., Chakrabarty, S., & Rizvi, M. A. (2021). Organoselenium compounds as acetylcholinesterase inhibitors: Evidence and mechanism of mixed inhibition. Journal of Physical Chemistry B, 125(6), 1531–1541. https://doi.org/10.1021/acs.jpcb.0c08111
Kumria, R., Nair, A. B., Goomber, G., & Gupta, S. (2016). Buccal films of prednisolone with enhanced bioavailability. Drug Delivery, 23(2), 471–478. https://doi.org/10.3109/10717544.2014.920058
Lanquist, A. P., Gupta, S., Al-Afyouni, K. F., Al-Afyouni, M., Kodanko, J. J., & Turro, C. (2021). Trifluoromethyl substitution enhances photoinduced activity against breast cancer cells but reduces ligand exchange in Ru(II) complex †. https://doi.org/10.1039/d1sc03213e
Liew, S. K., Malagobadan, S., Arshad, N. M., & Nagoor, N. H. (2020). A review of the structure—activity relationship of natural and synthetic antimetastatic compounds. Biomolecules, 10(1), 1–28. https://doi.org/10.3390/biom10010138
Lobo, S. (2020). Is there enough focus on lipophilicity in drug discovery? Expert Opinion on Drug Discovery, 15(3), 261–263. https://doi.org/10.1080/17460441.2020.1691995
Ma, R., Guo, D.-X., Li, H.-F., Liu, H.-X., Zhang, Y.-R., Ji, J.-B., Xing, J., & Wang, S.-Q. (2019). Spectroscopic methodologies and molecular docking studies on the interaction of antimalarial drug piperaquine and its metabolites with human serum albumin. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 222, 117158. https://doi.org/https://doi.org/10.1016/j.saa.2019.117158
Maddila, S., Gorle, S., Sampath, C., & Lavanya, P. (2016). Synthesis and anti-inflammatory activity of some new 1,3,4-thiadiazoles containing pyrazole and pyrrole nucleus. Journal of Saudi Chemical Society, 20, S306–S312. https://doi.org/10.1016/j.jscs.2012.11.007
Madibone, K. S., Deshmukh, P. P., Navalkar, A., Maji, S. K., Badani, P. M., & Manjare, S. T. (2020). Cyclic Organoselenide BODIPY-Based Probe: Targeting Superoxide in MCF-7 Cancer Cells. ACS Omega, 5(23), 14186–14193. https://doi.org/10.1021/acsomega.0c02074
Malik, M. A., Dar, O. A., Gull, P., Wani, M. Y., & Hashmi, A. A. (2018). Heterocyclic Schiff base transition metal complexes in antimicrobial and anticancer chemotherapy. MedChemComm, 9(3), 409–436. https://doi.org/10.1039/c7md00526a
Marrs, W., & Stella, N. (2009). Measuring Endocannabinoid Hydrolysis: Refining our Tools and Understanding. AAPS, 11(No.2). https://doi.org/10.1208/s12248-009-9109-0
Martínez, M., Carranza, M. P., Massaguer, A., Santos, L., Organero, J. A., Aliende, C., De Llorens, R., Ng-Choi, I., Feliu, L., Planas, M., Rodríguez, A. M., Manzano, B. R., Espino, G., & Jalón, F. A. (2017). Synthesis and Biological Evaluation of Ru(II) and Pt(II) Complexes Bearing Carboxyl Groups as Potential Anticancer Targeted Drugs. Inorganic Chemistry, 56(22), 13679–13696. https://doi.org/10.1021/acs.inorgchem.7b01178
Mata, A. M. O. F. da, Carvalho, R. M. de, Alencar, M. V. O. B. de, Cavalcante, Melo, A. A. de C., & Silva, B. B. da. (2016). Ascorbic Acid in the Prevention and Treatment of Cancer. 62(7), 680–686. https://doi.org/10.1590/1806-9282.62.07.680
Mehta, N., Aggarwal, S., Thareja, S., Malla, P., Misra, M., Bhardwaj, T. R., & Kumar, M. (2010). Synthesis, pharmacological and toxicological evaluation of amide derivatives of ibuprofen. International Journal of ChemTech Research, 2(1), 233–238.
Mian, P., van den Anker, J. N., van Calsteren, K., Annaert, P., Tibboel, D., Pfister, M., Allegaert, K., & Dallmann, A. (2020). Physiologically Based Pharmacokinetic Modeling to Characterize Acetaminophen Pharmacokinetics and N-Acetyl-p-Benzoquinone Imine (NAPQI) Formation in Non-Pregnant and Pregnant Women. Clinical Pharmacokinetics, 59(1), 97–110. https://doi.org/10.1007/s40262-019-00799-5
Mihailović, N., Marković, V., Matić, I. Z., Stanisavljević, N. S., Jovanović, Ž. S., Trifunović, S., & Joksović, L. (2017). Synthesis and antioxidant activity of 1,3,4-oxadiazoles and their diacylhydrazine precursors derived from phenolic acids. RSC Advances, 7(14), 8550–8560. https://doi.org/10.1039/C6RA28787E
Minimal Inhibitory Concentration (MIC). (2021). https://bio.libretexts.org/@go/page/11954
Mittapally, S., Taranum, R., & Parveen, S. (2018). Metal ions as antibacterial agents. Journal of Drug Delivery and Therapeutics, 8, 411–419. https://doi.org/9http://dx.doi.org/10.22270/jddt.v8i6-s.2063
Motwani, M. P., Bennett, F., Norris, P. C., Maini, A. A., George, M. J., Newson, J., Henderson, A., Hobbs, A. J., Tepper, M., White, B., Serhan, C. N., Macallister, R., & Gilroy, D. W. (2018). Potent Anti-Inflammatory and Pro-Resolving Effects of Anabasum in a Human Model of Self-Resolving Acute Inflammation. 104(4), 675–686. https://doi.org/10.1002/cpt.980
Mugesh, G., du Mont, W.-W., & Sies, H. (2001). Chemistry of Biologically Important Synthetic Organoselenium Compounds. Chemical Reviews, 101(7), 2125–2180. https://doi.org/10.1021/cr000426w
Mumtaz, A., Arshad, J., Saeed, A., Azhar, M., Nawaz, H., Iqbal, J., Nawaz, M. A. H., & Iqbal, J. (2018). Synthesis, characterization and urease inhibition studies of transition metal complexes of thioureas bearing ibuprofen moiety. Journal of the Chilean Chemical Society, 63(2), 3934–3940. https://doi.org/10.4067/s0717-97072018000203934
Mumtaz, A., Shoaib, M., Zaib, S., Shah, M. S., Bhatti, H. A., Saeed, A., Hussain, I., & Iqbal, J. (2018). Synthesis, molecular modelling and biological evaluation of tetrasubstituted thiazoles towards cholinesterase enzymes and cytotoxicity studies. Bioorganic Chemistry, 78(2), 141–148. https://doi.org/10.1016/j.bioorg.2018.02.024
Murahari, M., Mahajan, V., Neeladri, S., Kumar, M. S., & Mayur, Y. C. (2019). Ligand based design and synthesis of pyrazole based derivatives as selective COX-2 inhibitors. Bioorganic Chemistry, 86, 583–597. https://doi.org/https://doi.org/10.1016/j.bioorg.2019.02.031
Nandanwar, S. K., & Kim, H. J. (2019). Anticancer and Antibacterial Activity of Transition Metal Complexes. ChemistrySelect, 4(5), 1706–1721. https://doi.org/https://doi.org/10.1002/slct.201803073
Narsinghani, T., & Sharma, R. (2017). Synthesis, anti-inflammatory activities and docking studies of amide derivatives of meclofenamic acid. Chemical Papers, 71(4), 857–868. https://doi.org/10.1007/s11696-016-0102-7
Nayak, S., Gaonkar, S. L., Musad, E. A., & Dawsar, A. M. AL. (2021). 1,3,4-Oxadiazole-containing hybrids as potential anticancer agents: Recent developments, mechanism of action and structure-activity relationships. Journal of Saudi Chemical Society, 25(8), 101284. https://doi.org/10.1016/j.jscs.2021.101284
Njus, D., Kelley, P. M., Tu, Y.-J., & Schlegel, H. B. (2020). Ascorbic Acid: The Chemistry Underlying Its Antioxidant Properties. Free Radical Biology and Medicine, 159, 37–43. https://doi.org/https://doi.org/10.1016/j.freeradbiomed.2020.07.013
Novilla, A., Mustofa, M., Astuti, I., Jumina, J., & Suwito, H. (2019). Cytotoxic Activity of Methoxy-4’amino Chalcone Derivatives Against Leukemia Cell Lines. Molecular and Cellular Biomedical Sciences, 3(1), 34. https://doi.org/10.21705/mcbs.v3i1.44
Ohashi, N., & Kohno, T. (2020). Analgesic Effect of Acetaminophen: A Review of Known and Novel Mechanisms of Action. Frontiers in Pharmacology, 11(November), 1–6. https://doi.org/10.3389/fphar.2020.580289
Olszewska, P., Cal, D., Zagórski, P., & Mikiciuk-Olasik, E. (2020). A novel trifluoromethyl 2-phosphonopyrrole analogue inhibits human cancer cell migration and growth by cell cycle arrest at G1 phase and apoptosis. European Journal of Pharmacology, 871(September 2019). https://doi.org/10.1016/j.ejphar.2020.172943
Osowole, A. A., Agbaje, O. B. A., & Ojo, B. O. (2014). Synthesis , characterization and antibacterial properties of some heteroleptic metal ( II ) complexes of paracetamol and vanillin. Asian Journal of Pharmaceutical and Clinical Research, 7(3).
Ouellette, R. J., & Rawn, J. D. (2018). 24 - Amines and Amides (R. J. Ouellette & J. D. B. T.-O. C. (Second E. Rawn (Eds.); pp. 763–800). Academic Press. https://doi.org/https://doi.org/10.1016/B978-0-12-812838-1.50024-4
Ozawa, M., Kubo, T., Lee, S. H., & Oe, T. (2019). LC-MS analyses of N -acetyl- p -benzoquinone imine-adducts of glutathione , cysteine , N -acetylcysteine , and albumin in a plasma sample : A case study from a patient with a rare acetaminophen-induced acute swelling rash. J. Toxical. Sci, 44(8), 559–563. https://doi.org/https://doi.org/10.2131/jts.44.559
Paul, E. D., Dallatu, Y. A., & Akwu, F. J. (2018). Antimicrobial, Acute Toxicity and Anti-inflammatory Investigations of Mg(II) Complex of Acetaminophen. 3(2), 959–963.
Pérez, D. J., Díaz-Reval, M. I., Obledo-Benicio, F., Zakai, U. I., Gómez-Sandoval, Z., Razo-Hernández, R. S., West, R., Sumaya-Martínez, M. T., Pineda-Urbina, K., & Ramos-Organillo, Á. (2017). Silicon containing ibuprofen derivatives with antioxidant and anti-inflammatory activities: An in vivo and in silico study. European Journal of Pharmacology, 814, 18–27. https://doi.org/10.1016/j.ejphar.2017.07.046
Permala, J., Tarning, J., Nosten, F., & White, N. J. (2017). Prediction of Improved Antimalarial Chemoprevention with Weekly Dosing. Antimicrobial Agents and Chemotherapy, 61(5), e02491-16.
Ragab, F. A., Heiba, H. I., El-Gazzar, M. G., Abou-Seri, S. M., El-Sabbagh, W. A., & El-Hazek, R. M. (2016). Synthesis of novel thiadiazole derivatives as selective COX-2 inhibitors. MedChemComm, 7(12), 2309–2327. https://doi.org/10.1039/c6md00367b
Ragab, F. A., Heiba, H. I., El-Gazzar, M. G., Abou-Seri, S. M., El-Sabbagh, W. A., & El-Hazek, R. M. (2017). Anti-inflammatory, analgesic and COX-2 inhibitory activity of novel thiadiazoles in irradiated rats. Journal of Photochemistry and Photobiology B: Biology, 166, 285–300. https://doi.org/10.1016/j.jphotobiol.2016.12.007
Ramachandran, A., & Jaeschke, H. (2019). Acetaminophen Hepatotoxicity. Semin Liver Dis, 39, 221–234. https://doi.org/10.1055/s-0039-1679919
Rashid, M., Rafique, H., Roshan, S., Shamas, S., Iqbal, Z., Ashraf, Z., Abbas, Q., Hassan, M., Ur, Z., Qureshi, R., Hassham, M., Asad, H. Bin, & Com, M. (2020). Enzyme Inhibitory Kinetics and Molecular Docking Studies ofHalo-Substituted Mixed Ester/Amide-Based Derivatives as JackBean Urease Inhibitors. https://doi.org/10.1155/2020/8867407
Rasmussen, S. A., Ceja, F. G., Conrad, M. D., Tumwebaze, P. K., Byaruhanga, O., Katairo, T., Nsobya, S. L., Rosenthal, P. J., & Cooper, A. (2017). crossm Changing Antimalarial Drug Sensitivities in Uganda.
Rizvi, F., Khan, M., Jabeen, A., Siddiqui, H., & Choudhary, M. I. (2019). Studies on Isoniazid Derivatives through a Medicinal Chemistry Approach for the Identification of New Inhibitors of Urease and Inflammatory Markers. Scientific Reports, 9(1), 1–14. https://doi.org/10.1038/s41598-019-43082-0
Rizzotto, M. (2012). Metal Complexes as Antimicrobial Agents. In V. Bobbarala (Ed.), A Search for Antibacterial Agents (Teodora Sm, pp. 74–89). InTech. https://doi.org/10.5772/45651
Roberts, E., Nunes, V. D., Buckner, S., Latchem, S., Constanti, M., Miller, P., Doherty, M., Zhang, W., Birrell, F., Porcheret, M., Dziedzic, K., Bernstein, I., Wise, E., & Conaghan, P. G. (2016). Paracetamol: Not as safe as we thought? A systematic literature review of observational studies. Annals of the Rheumatic Diseases, 75(3), 552–559. https://doi.org/10.1136/annrheumdis-2014-206914
Sangcharoen, N., Klaypradit, W., & Wilaipun, P. (2017). Antimicrobial activity optimization of nisin, ascorbic acid and ethylenediamine tetraacetic acid disodium salt (EDTA) against Salmonella Enteritidis ATCC 13076 using response surface methodology. Agriculture and Natural Resources, 51(5), 355–364. https://doi.org/https://doi.org/10.1016/j.anres.2017.12.005
Santis, M. De, & Saad, F. (2016). Corticosteroids in the Treatment of Metastatic Castration-resistant Prostate Cancer. Urology, 96, 156–164. https://doi.org/10.1016/j.urology.2016.02.010
Sasso, O., Migliore, M., Habrant, D., Armirotti, A., Albani, C., Summa, M., Moreno-sanz, G., Scarpelli, R., & Piomelli, D. (2015). Multitarget fatty acid amide hydrolase / cyclooxygenase blockade suppresses intestinal in fl ammation and protects against nonsteroidal anti-in fl ammatory drug-dependent gastrointestinal damage. FASEB, 29(6), 2616–2627. https://doi.org/https://doi.org/10.1096/fj.15-270637
Scarpelli, R., Sasso, O., & Piomelli, D. (2016). A Double Whammy : Targeting Both Fatty Acid Amide Hydrolase (FAAH) and Cyclooxygenase (COX) To Treat Pain and Inflammation. ChemMedChem, 11(12), 1242–1251. https://doi.org/10.1002/cmdc.201500395
Scattolin, T., Bortolamiol, E., Visentin, F., Palazzolo, S., Caligiuri, I., Perin, T., Canzonieri, V., Demitri, N., Rizzolio, F., & Togni, A. (2020). Palladium(II)‐η 3 ‐Allyl Complexes Bearing N ‐Trifluoromethyl N ‐Heterocyclic Carbenes: A New Generation of Anticancer Agents that Restrain the Growth of High‐Grade Serous Ovarian Cancer Tumoroids. Chemistry – A European Journal, 26(51), 11868–11876. https://doi.org/10.1002/chem.202002199
Seraj, F., Mohammed Khan, K., Khan, A., Ali, M., Khalil, R., Ul-Haq, Z., Hameed, S., Taha, M., Salar, U., & Perveen, S. (2021). Biology-oriented drug synthesis (BIODS), in vitro urease inhibitory activity, and in silico studies on ibuprofen derivatives. Molecular Diversity, 25, 143–157. https://doi.org/10.1007/s11030-019-10032-x
Shakeel, A. (2016). Thiourea Derivatives in Drug Design and Medicinal Chemistry: A Short Review. Journal of Drug Design and Medicinal Chemistry, 2(1), 10. https://doi.org/10.11648/j.jddmc.20160201.12
Shenoy, N., Creagan, E., Witzig, T., & Levine, M. (2018). Ascorbic Acid in Cancer Treatment: Let the Phoenix Fly. Cancer Cell, 34(5), 700–706. https://doi.org/10.1016/j.ccell.2018.07.014
Shetty, A., & Dick, T. (2018). Mycobacterial Cell Wall Synthesis Inhibitors Cause Lethal ATP Burst. 9(August), 1–9. https://doi.org/10.3389/fmicb.2018.01898
Shoaib, M., Hussain, H., Shah, S. W. A., Umar, M. N., & Ullah, A. (2017). Synthesis, acute toxicity, analgesic activity & cytotoxicity of Some bisthiourea derivatives. Pakistan Journal of Pharmaceutical Sciences, 30(4), 1351–1356.
Singh, B. R., Yadav, A., & Ravichandran, K. (2021). Comparative Antimicrobial Activity of Aspirin , Paracetamol , Flunixin Meglumine , Tolfenamic Acid , Diclofenac Sodium and Pheniramine Maleate . Acta Scientific Veterinary Sciences Acta Scientific Veterinary Sciences ( ISSN : 2582-3183 ) Comparative Antim. Acta Scientific Veterinary Science, 3(September), 30–42.
Siwach, A., & Verma, P. K. (2020). Therapeutic potential of oxadiazole or furadiazole containing compounds. BMC Chemistry, 14(1), 1–40. https://doi.org/10.1186/s13065-020-00721-2
Stratan, E., Ţurcan, N., Crudu, V., Romancenco, E., Cotelea, T., Niţulescu, G. M., Chiriţă, C., & Moruşciag, L. (2018). Biological evaluation of new 2-phenethylbenzoyl thiourea derivatives as antituberculosis agents. Farmacia, 66(1), 97–106.
Straub, R. H., & Cutolo, M. (2016). Glucocorticoids and chronic inflammation. 6–14. https://doi.org/10.1093/rheumatology/kew348
Syahri, J., Yuanita, E., Nurohmah, B. A., Armunanto, R., & Purwono, B. (2017). Chalcone analogue as potent anti-malarial compounds againstPlasmodiumfalciparum: Synthesis, biological evaluation, and docking simulation study. Asian Pacific Journal of Tropical Biomedicine, 7(8), 675–679. https://doi.org/10.1016/j.apjtb.2017.07.004
The Royal Society of Chemistry. (2017). Synthesis of paracetamol by acetylation. In Comprehensive Organic Chemistry Experiments for the Laboratory Classroom (p. 242).
Torfs, E., Piller, T., Cos, P., & Cappoen, D. (2019). Opportunities for Overcoming Mycobacterium tuberculosis Drug Resistance : Emerging Mycobacterial Targets and Host-Directed Therapy.
Turner, R. J. (2017). Metal-based antimicrobial strategies. Microbial Biotechnology, 10(5), 1062–1065. https://doi.org/10.1111/1751-7915.12785
Ullah, N., Huang, Z., Sanaee, F., Rodriguez-Dimitrescu, A., Aldawsari, F., Jamali, F., Bhardwaj, A., Islam, N. U., & Velázquez-Martínez, C. A. (2016). NSAIDs do not require the presence of a carboxylic acid to exert their anti-inflammatory effect – why do we keep using it? Journal of Enzyme Inhibition and Medicinal Chemistry, 31(6), 1018–1028. https://doi.org/10.3109/14756366.2015.1088840
Vedavathi, P., Sudhamani, H., & Raju, C. N. (2017). Synthesis and antimicrobial activity of new urea and thiourea derivatives of (2′-(1H-tetrazol-5-yl)biphenyl-4-yl)methanamine. Research on Chemical Intermediates, 43(5), 3251–3263. https://doi.org/10.1007/s11164-016-2823-1
Verghese, R. J., Mathew, S. K., & David, A. (2018). Antimicrobial activity of Vitamin C demonstrated on uropathogenic Escherichia coli and Klebsiella pneumoniae. Current Research in Scientific Medicine, 3(2), 88–93. https://doi.org/10.4103/jcrsm.jcrsm
Wang, H., Zhai, Z.-W., Shi, Y.-X., Tan, C.-X., Weng, J.-Q., Han, L., Li, B.-J., & Liu, X.-H. (2019). Novel Trifluoromethylpyrazole Acyl Thiourea Derivatives: Synthesis, Antifungal Activity and Docking Study. Letters in Drug Design & Discovery, 16(7), 785–791. https://doi.org/10.2174/1570180815666180704103047
Yadav, A., Mohite, S., & Magdum, C. (2020). Synthesis, Characterization and Biological Evaluation of Some Novel 1,3,4-Oxadiazole Derivatives as Potential Anticancer Agents. International Journal of Scientific Research in Science and Technology, 275–282. https://doi.org/10.32628/IJSRST207234
Zhang, J., Tan, Y., Li, G., Chen, L., Nie, M., Wang, Z., & Ji, H. (2021). Coumarin Sulfonamides and Amides Derivatives: Design, Synthesis, and Antitumor Activity In Vitro. Molecules, 26(4), 786. https://doi.org/10.3390/molecules26040786
Zuegg, J., Solutions, S., Frei, S. A., Blaskovich, M. A. T., Willans, C. E., Wilson, J. J., & Cooper, A. (2020). Metal complexes as a promising source for new antibiotics. Chemical Science, 11, 2627–2639. https://doi.org/10.1039/c9sc06460e