Synthesis and study of antimicrobial activity of some tetrahydrocarbazole derivatives substituted with NSAID

Mustafa H. Mahdi; Ashour H. Dawood; Dhurgham Q. Shaheed

doi:10.32947/ajps.v22i2.857

Authors

Mustafa H. Mahdi Babylon Health Directorate, Iraq
Ashour H. Dawood Al-Esraa University College, Baghdad-Iraq
Dhurgham Q. Shaheed College of Pharmacy, University of Alkafeel, Najaf-Iraq

DOI:

https://doi.org/10.32947/ajps.v22i2.857

Keywords:

Tetrahydrocarbazole,non-steroidal anti-inflammatory drug,Molecular Docking, antimicrobial activity

Abstract

New tetrahydrocarbazole derivatives substituted at the heteroatom (N) by non-steroidal anti-inflammatory drug (NSAIDs) were synthesized by reaction of cyclohehexanon (C.H.N.) with phenyl hydrazine (P.H.Z.) to form tetrahydrocarbazole (THCZ), where the latter is reacted with NSAID (Ketoprofen) via amide bond to yield

substituted THCZ, compounds chemical structures were verified by: 1H, 13C NMR and FTIR spectroscopy.

Antifungal activity of the synthesized compounds was investigated by docking study and in vitro test to reveal good antifungal activity, but the in vitro test also showed that the compounds have weak to moderate antibacterial activity.

References

Farha MA, Brown ED. Drug repurposing for antimicrobial discovery. Nature microbiology. 2019;4(4):565-77. DOI: https://doi.org/10.1038/s41564-019-0357-1

Salih N, Salimon J, Yousif E. Synthesis and antimicrobial activities of 9H-carbazole derivatives. Arabian Journal of Chemistry. 2016;9: S781-S6. DOI: https://doi.org/10.1016/j.arabjc.2011.08.013

Chaudhari TY, Tandon V. Recent approaches to the synthesis of tetrahydrocarbazoles. Organic & Biomolecular Chemistry. 2021;19(9):1926-39. DOI: https://doi.org/10.1039/D0OB02274H

Padmavathi S, Tajne MR. Design, synthesis, molecular docking studies and anti-microbial activity of novel 1, 2, 3, 4-tetrahydrocarbazole derivatives. International Current Pharmaceutical Journal. 2016;5(9):73-8. DOI: https://doi.org/10.3329/icpj.v5i9.29231

Bublitz M, Kjellerup L, Cohrt KOH, Gordon S, Mortensen AL, Clausen JD, et al. Tetrahydrocarbazoles are a novel class of potent P-type ATPase inhibitors with antifungal activity. PloS one. 2018;13(1): e0188620. DOI: https://doi.org/10.1371/journal.pone.0188620

Sellamuthu S, Gutti G, Kumar D, Kumar Singh S. Carbazole: A Potent Scaffold for Antitubercular Drugs. Mini-Reviews in Organic Chemistry. 2018;15(6):498-507. DOI: https://doi.org/10.2174/1570193X15666180220141342

Gupta A, Kalantar-Zadeh K, Reddy ST. Ramatroban as a Novel Immunotherapy for COVID-19. Journal of molecular and genetic medicine: an international journal of biomedical research. 2020;14(3). DOI: https://doi.org/10.37421/jmgm.2020.14.457

Mohamed NA, El-Serwy WS, Abd El-Karim SS, Awad GE, Elseginy SA. Synthesis, antimicrobial evaluation, and molecular docking studies of new tetrahydrocarbazole derivatives. Research on Chemical Intermediates. 2016;42(2):1363-86. DOI: https://doi.org/10.1007/s11164-015-2090-6

Honarnejad K, Daschner A, Gehring A, Szybinska A, Giese A, Kuznicki J, et al. Identification of tetrahydrocarbazoles as novel multifactorial drug candidates for treatment of Alzheimer’s disease. Translational psychiatry. 2014;4(12): e489-e. DOI: https://doi.org/10.1038/tp.2014.132

Kumar N, Kumar V, Chowdhary Y. A review on synthesis methods of tricyclic 1, 2, 3, 4-tetrahydrocarbazoles. 2022.

Saravanabhavan M, Ebenazer AF, Murugesan V, Sekar M. Synthesis, Spectroscopic Characterization and Biological Evaluation of 1-(4'-Hydroxybenzamido)-Imine-1, 2, 3, 4-Tetrahydrocarbazole Derivatives. Journal of Advanced Physics. 2017;6(1):30-40. DOI: https://doi.org/10.1166/jap.2017.1286

Wang W, Dong G, Gu J, Zhang Y, Wang S, Zhu S, et al. Structure–activity relationships of tetrahydrocarbazole derivatives as antifungal lead compounds. MedChemComm. 2013;4(2):353-62. DOI: https://doi.org/10.1039/C2MD20211E

Mahdi MF, Dawood, A.H., Hussein, A.K., 2013. Design, Synthesis and Preliminary Pharmacological Evaluation of Mutual Prodrug of Non-Steroidal Anti-Inflammatory Drugs Coupling with Natural Anti-Oxidants Via Glycine. Al Mustansiriyah Journal of Pharmaceutical Sciences 13, 155–169. doi:10.32947/ajps. v13i1.211. DOI: https://doi.org/10.32947/ajps.v13i1.211

Chan EWL, Yee ZY, Raja I, Yap JKY. Synergistic effect of non-steroidal anti-inflammatory drugs (NSAIDs) on antibacterial activity of cefuroxime and chloramphenicol against methicillin-resistant Staphylococcus aureus. Journal of global antimicrobial resistance. 2017; 10:70-4. DOI: https://doi.org/10.1016/j.jgar.2017.03.012

Shah PN, Marshall-Batty KR, Smolen JA, Tagaev JA, Chen Q, Rodesney CA, et al. antimicrobial activity of ibuprofen against cystic fibrosis-associated gram-negative pathogens. Antimicrobial agents and chemotherapy. 2018;62(3): e01574-17. DOI: https://doi.org/10.1128/AAC.01574-17

Hadi HF. Comparison Between Two NSAIDs (Non selective & selective COX-2 Inhibitor) According to their Renal Toxicity on Elderly People. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2007;4(1):125-36. DOI: https://doi.org/10.32947/ajps.v4i1.387

Leão C, Borges A, Simões M. NSAIDs as a Drug Repurposing Strategy for Biofilm Control. Antibiotics. 2020;9(9):591. DOI: https://doi.org/10.3390/antibiotics9090591

Zimmermann P, Curtis N. Antimicrobial effects of antipyretics. Antimicrobial Agents and Chemotherapy. 2017;61(4): e02268-16. DOI: https://doi.org/10.1128/AAC.02268-16

Alwan AH, Abas SM. Study the Relationship Between the Ability of Biofilms Formation and Antibiotic Sensitivity for Klebsiella pneumonia Isolated from Different Clinical Sources. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2016;16(1):1-9. DOI: https://doi.org/10.32947/ajps.v16i1.89

Borsche-Drechsel Reaction. Comprehensive Organic Name Reactions and Reagents. p. 471-3.

Al-Naimi K, Alwahb HA. Synthesis of Some New Amides Derived from Indomethacin. JOURNAL OF EDUCATION AND SCIENCE. 2013;26(5):105-12. DOI: https://doi.org/10.33899/edusj.2013.163060

Al-Majidi SM, Al-Quaz AM. SYNTHESIS OF SOME NEW N-SUBSTITUTED-1, 2, 3, 4-TETRAHYDROCARBAZOLE DERIVATIVES AND STUDY THEIR BIOLOGICALACTIVITY. Al-Nahrain Journal of Science. 2010;13(1):26-35. DOI: https://doi.org/10.22401/JNUS.13.1.04

Rogers CU, Corson BB. One-Step Synthesis of 1,2,3,4-Tetrahydrocarbazole and 1,2-Benzo-3,4-dihydrocarbazole. Journal of the American Chemical Society. 1947;69(11):2910-1. DOI: https://doi.org/10.1021/ja01203a506

Hargrove TY, Friggeri L, Wawrzak Z, Qi A, Hoekstra WJ, Schotzinger RJ, et al. Structural analyses of Candida albicans sterol 14α-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis. Journal of Biological Chemistry. 2017;292(16):6728-43. DOI: https://doi.org/10.1074/jbc.M117.778308

Perveen S, Chaudhary HS. In silico screening of antibacterial compounds from herbal sources against Vibrio cholerae. Pharmacognosy magazine. 2015;11(Suppl 4): S550. DOI: https://doi.org/10.4103/0973-1296.172960

Zhu S-P, Wang W-Y, Fang K, Li Z-G, Dong G-Q, Miao Z-Y, et al. Design, synthesis and antifungal activity of carbazole derivatives. Chinese Chemical Letters. 2014;25(2):229-33. DOI: https://doi.org/10.1016/j.cclet.2013.10.022

Lepesheva GI, Waterman, M.R., 2007. Sterol 14α-demethylase cytochrome P450 (CYP51), a P450 in all biological kingdoms. Biochimica et Biophysica Acta (BBA) - General Subjects 1770, 467–477. doi: 10.1016/j.bbagen.2006.07.018. DOI: https://doi.org/10.1016/j.bbagen.2006.07.018