Design, Synthesis and Anti-Bacterial Activity Evaluation of Indole-Based Benzophenone and Their Derivatives

Anahtar Kelimeler:

Staphylococcus aureus and Escherichia coli, Staphylococcus aureus and Escherichia coli, Staphylococcus aureus and Escherichia coli, Escherichia coli, Staphylococcus aureus

Design, Synthesis and Anti-Bacterial Activity Evaluation of Indole-Based Benzophenone and Their Derivatives

Indole and benzophenone moiety are of significant interest to investigators because they are found in many natural products and pharmacologically active compounds. They represent versatile synthetic building blocks. The benzophenone and indole scaffolds are special structures in medicinal chemistry because these compounds are found in several biologically active natural products, compounds containing indole and benzophenone exhibit anticancer, antiinflammatory, antimicrobial, and antiviral activities. In this study, derivatives of 2-(diphenyl methylene) hydrazine, containing both indole and benzophenone moieties were successfully synthesized. The structural elucidation of the synthesized compounds were done using spectroscopic techniques like IR, 1HNMR, and 13CNMR. The synthesized target compounds were investigated for their in vitro antibacterial activity against two bacterial strains; staphylococcus aureus (S. auras), and Escherichia coli (E. coli) using the disc diffusion method. All synthesized target compounds showed no significant activity against Staphylococcus aureus (S. aureus) but exhibited moderate activity against Escherichia coli (E. coli). Among all the synthesized compounds, 2-(diphenyl methylene)-1-((1-tosyl-1H-indol-3-yl) methylene) hydrazine (BHT) (7b) showed a good inhibition at a concentration of 50 μg/mL with a zone of inhibition of 21.7 mm against Escherichia coli (E.coli) which was comparable with standard drug Ceftriaxone with the zone of inhibition of 26 mm. Thus, this compound could be considered as a lead molecule to design and develop novel antibacterial drugs.

Keywords:

antibacterial, benzophenone, indole, synthesis,

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1. Al-Wabli RI, Alsulami MA, Bukhari SI, Moubayed NM, Al-Mutairi MS, Attia MI. Design, synthesis, and antimicrobial activity of certain new Indole-1, 2, 4 Triazole conjugates. Molecules. 2021 Apr 15;26(8):2292.
2. Xue YJ, Li MY, Jin XJ, Zheng CJ, Piao HR. Design, synthesis and evaluation of carbazole derivatives as potential antimicrobial agents. Journal of Enzyme Inhibition and Medicinal Chemistry. 2021 Jan 1;36(1):296-307.
3. Carullo G, Mazzotta S, Giordano F, Aiello F. Green Synthesis of New Pyrrolo [1, 2-a] quinoxalines as Antiproliferative Agents in GPER-expressing Breast Cancer Cells. Journal of Chemistry. 2021 Oct 31;2021.
4. Kaur J, Utreja D, Jain N, Sharma S. Recent developments in the synthesis and antimicrobial activity of indole and its derivatives. Current Organic Synthesis. 2019 Jan 1;16(1):17-37.
5. Inman M, Moody CJ. Indole synthesis–something old, something new. Chemical Science. 2013; 4(1):29-41.
6. MahamadAlli Shaikh T, Debebe H. Synthesis and evaluation of antimicrobial activities of novel N-substituted indole derivatives. Journal of Chemistry. 2020 Apr 14; 2020
7. Raju PA, Mallikarjunarao R, Gopal KV, Sreeramulu J, Reddy DM, Krishnamurthi KP, Reddy SR. Synthesis and biological activity of some new indole derivatives containing pyrazole moiety. J. Chem. Pharm. Res. 2013;5(10):21-7.
8. MahamadAlli Shaikh T, Debebe H. Synthesis and evaluation of antimicrobial activities of novel N-substituted indole derivatives. Journal of Chemistry. 2020 Apr 14;2020.
9. Gupta AK, Sharma M. Synthesis, Characterization and Anti-Microbial Activity of Indole Derivatives. Journal of Drug Delivery and Therapeutics. 2019 Aug 25;9(4-s):918-25.
10. Ibrahim M, Taha M, Almandil NB, Kawde AN, Nawaz M. Synthesis, characterization and electrochemical properties of some biologically important indole-based-sulfonamide derivatives. BMC chemistry. 2020 Dec;14(1):1-0.
11. Tiwari S, Kirar S, Banerjee UC, Neerupudi KB, Singh S, Wani AA, Bharatam PV, Singh IP. Synthesis of N-substituted indole derivatives as potential antimicrobial and antileishmanial agents. Bioorganic Chemistry. 2020 Jun 1;99:103787.
12. Shirinzadeh H, Süzen S, Altanlar N, Westwell AD. Antimicrobial activities of new indole derivatives containing 1, 2, 4-triazole, 1, 3, 4-thiadiazole and carbothioamide. Turkish Journal of Pharmaceutical Sciences. 2018 Dec;15(3):291.
13. Mane YD, Sarnikar YP, Surwase SM, Biradar DO, Gorepatil PB, Shinde VS, Khade BC. Design, synthesis, and antimicrobial activity of novel 5-substituted indole-2-carboxamide derivatives. Research on Chemical Intermediates. 2017 Feb;43(2):1253-75.
14. Pecnard S, Hamze A, Bignon J, Prost B, Deroussent A, Gallego-Yerga L, Peláez R, Paik JY, Diederich M, Alami M, Provot O. Anticancer properties of indole derivatives as IsoCombretastatin A-4 analogues. European Journal of Medicinal Chemistry. 2021 Nov 5;223:113656.
15. Ma J, Li J, Guo P, Liao X, Cheng H. Synthesis and antitumor activity of novel indole derivatives containing α-aminophosphonate moieties. Arabian Journal of Chemistry. 2021 Aug 1;14(8):103256.
16. Dorababu A. Indole–a promising pharmacophore in recent antiviral drug discovery. RSC Medicinal Chemistry. 2020; 11(12):1335-53.
17. Xue S, Ma L, Gao R, Li Y, Li Z. Synthesis and antiviral activity of some novel indole-2-carboxylate derivatives. Acta Pharmaceutica Sinica B. 2014 Aug 1;4(4):313-21.
18. Solanki D, Nakra VK, Tiwari A, Gupta AK, Gandhi S. Synthesis, characterization and anti-inflammatory activity of novel 1, 5-disubstituted indole derivatives. European Journal of Molecular & Clinical Medicine. 2020;7(11):4622-35.
19. Abdellatif KR, Lamie PF, Omar HA. 3-Methyl-2-phenyl-1-substituted-indole derivatives as indomethacin analogs: design, synthesis and biological evaluation as potential anti-inflammatory and analgesic agents. Journal of Enzyme Inhibition and Medicinal Chemistry. 2016 Mar 3; 31(2):318-24.
20. Al-Ghorbani M, Lakshmi Ranganatha V, Prashanth T, Begum B, Khanum SA. In vitro antibacterial and antifungal evaluation of some benzophenone analogues. Der Pharma Chem. 2013;5:269-73.
21. Bushra Begum A, Khanum NF, Ranganatha VL, Prashanth T, Al-Ghorbani M, Khanum SA. Evaluation of Benzophenone-N-Ethyl morpholine ethers as antibacterial and antifungal activities. Journal of Chemistry. 2014 Jan 28;2014.
22. Zhang S, An B, Yan J, Huang L, Li X. The synthesis and evaluation of new benzophenone derivatives as tubulin polymerization inhibitors. RSC advances. 2016;6(91):88453-62.
23. Cortez-Maya S, Cortes Cortes E, Hernández-Ortega S, Apan TR, Martínez-García M. Synthesis of 2-aminobenzophenone derivatives and their anticancer activity. Synthetic Communications. 2012 Jan 1;42(1):46-54.
24. Gulnaz AR, Mohammed YH, Khanum SA. Design, synthesis and molecular docking of benzophenone conjugated with oxadiazole sulphur bridge pyrazole pharmacophores as anti inflammatory and analgesic agents. Bioorganic Chemistry. 2019 Nov 1; 92:103220.
25. Feng Z, Chen J, Feng L, Chen C, Ye Y, Lin L. Polyisoprenylated benzophenone derivatives from Garcinia cambogia and their anti-inflammatory activities. Food & Function. 2021;12(14):6432-41.
26. Shirinzadeh H, Altanlar N, Yucel N, Ozden S, Suzen S. Antimicrobial evaluation of indole-containing hydrazone derivatives. Zeitschrift für Naturforschung C. 2011 Aug 1;66(7-8):340-4.
27. Hoda S, Vijayaraghavan P. Evaluation of antimicrobial prospective of Parmotrema perlatum hexane extract. Int J Pharm Res Allied Sci. 2015 Jan 1;4(2):47-53.