Main Article Content

Azni Izwati Hamdan
Dike Dandari Sukmana
Norsyafikah Asyilla Nordin


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.


Download data is not yet available.

Article Details

How to Cite
Review Articles


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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

Ansari, A., Ali, A., Asif, M., & Shamsuzzaman. (2017). Review: biologically active pyrazole derivatives. New Journal of Chemistry, 41(1), 16–41.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

Biotechnology, N. C. for. (n.d.). Prednisolone. PubChem Compound. 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.

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.

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.

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.

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.

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.

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).

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).

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.

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.

Dinarello, C. A. (2010). Anti-inflammatory Agents: Present and Future. Cell, 140(6), 935–950.

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.

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.

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.

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).

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.

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.

Glomb, T., & Świątek, P. (2021). Antimicrobial Activity of 1,3,4-Oxadiazole Derivatives. International Journal of Molecular Sciences, 22(13), 6979.

Glomb, T., Szymankiewicz, K., & Świątek, P. (2018). Anti-Cancer Activity of Derivatives of 1,3,4-Oxadiazole. Molecules, 23(12), 3361.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Hughes, J. P., Rees, S., Kalindjian, S. B., Philpott, K. L., Philpott, K., & Building, H. (2011). Principles of early drug discovery Correspondence.

Ibuprofen Synthesis – Writing Anthology. (n.d.). Retrieved March 22, 2021, from

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.

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.

Kafarski, P., & Talma, M. (2018). Recent advances in design of new urease inhibitors: A review. Journal of Advanced Research, 13, 101–112.

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.

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.

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).

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.

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.

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.

Kumria, R., Nair, A. B., Goomber, G., & Gupta, S. (2016). Buccal films of prednisolone with enhanced bioavailability. Drug Delivery, 23(2), 471–478.

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 †.

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.

Lobo, S. (2020). Is there enough focus on lipophilicity in drug discovery? Expert Opinion on Drug Discovery, 15(3), 261–263.

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.

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.

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.

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.

Marrs, W., & Stella, N. (2009). Measuring Endocannabinoid Hydrolysis: Refining our Tools and Understanding. AAPS, 11(No.2).

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.

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.

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.

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.

Minimal Inhibitory Concentration (MIC). (2021).

Mittapally, S., Taranum, R., & Parveen, S. (2018). Metal ions as antibacterial agents. Journal of Drug Delivery and Therapeutics, 8, 411–419.

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.

Mugesh, G., du Mont, W.-W., & Sies, H. (2001). Chemistry of Biologically Important Synthetic Organoselenium Compounds. Chemical Reviews, 101(7), 2125–2180.

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.

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.

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.

Nandanwar, S. K., & Kim, H. J. (2019). Anticancer and Antibacterial Activity of Transition Metal Complexes. ChemistrySelect, 4(5), 1706–1721.

Narsinghani, T., & Sharma, R. (2017). Synthesis, anti-inflammatory activities and docking studies of amide derivatives of meclofenamic acid. Chemical Papers, 71(4), 857–868.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

Ramachandran, A., & Jaeschke, H. (2019). Acetaminophen Hepatotoxicity. Semin Liver Dis, 39, 221–234.

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.

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.

Rizzotto, M. (2012). Metal Complexes as Antimicrobial Agents. In V. Bobbarala (Ed.), A Search for Antibacterial Agents (Teodora Sm, pp. 74–89). InTech.

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.

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.

Santis, M. De, & Saad, F. (2016). Corticosteroids in the Treatment of Metastatic Castration-resistant Prostate Cancer. Urology, 96, 156–164.

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.

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.

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.

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.

Shakeel, A. (2016). Thiourea Derivatives in Drug Design and Medicinal Chemistry: A Short Review. Journal of Drug Design and Medicinal Chemistry, 2(1), 10.

Shenoy, N., Creagan, E., Witzig, T., & Levine, M. (2018). Ascorbic Acid in Cancer Treatment: Let the Phoenix Fly. Cancer Cell, 34(5), 700–706.

Shetty, A., & Dick, T. (2018). Mycobacterial Cell Wall Synthesis Inhibitors Cause Lethal ATP Burst. 9(August), 1–9.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.