BIOLOGICAL EVALUATION, QSAR AND MOLECULAR MODELING STUDIES OF 2,4-DICHLOROBENZOIC ACID DERIVATIVES AS ANTIMICROBIAL AGENTS
Objective: The aim of this study was to evaluate 2,4-dichlorobenzoic acid derivatives as antimicrobial agents through in vitro, QSAR and molecular docking studies.
Methods: The compounds were subjected to in vitro antimicrobial screening by test tube dilution method and the structural characteristics governing the antimicrobial potential were studied using QSAR methodology. These compounds were also screened for docking simulation to find out binding confirmation of reported compounds with PDB 1aj0 and 5fsa using AutoDock tools and discovery studio.
Results: The antimicrobial evaluation data indicated that compounds 13 and 18 were found to be the most effective against all the bacterial strains and Aspergillus niger while compounds 1 and 14 exhibited more antifungal potential against Candida albicans. QSAR studies confirmed the role of molar refractivity and Balaban index (J) as controlling parameters for antimicrobial potential. Molecular modeling study revealed that compounds interact with the active site of PDB by hydrophobic, hydrogen bonding, and Van der Wall interactions.
Conclusion: These test compounds were identified as potent candidates for the control of microbial strains tested, and structural relationship with activity may provide valuable information for further design and synthesis of compounds with antimicrobial potential.
2. Thangaraj M, Gengan RM, Ranjan B, Muthusamy R. Synthesis, molecular docking, antimicrobial, antioxidant and toxicity assessment of quinoline peptides. J Photochem Photobiol B 2018;178:287-5.
3. Noreen M, Rasool N, Gull Y, Zahoor AF, Yaqoob A, Kousar S, et al. A facile synthesis of new 5-aryl-thiophenes bearing sulfonamide moiety via Pd (0)-catalyzed suzuki–miyaura cross coupling reactions and 5-bromothiophene-2-acetamide: As potent urease inhibitor, antibacterial agent and hemolytically active compounds. J Saudi Chem Soc 2017;21:S403-14.
4. Swain SS, Paidesetty SK, Padhy RN. Antibacterial activity, computational analysis and host toxicity study of thymol-sulfonamide conjugates. Biomed Pharmacother 2017;88:181-93.
5. Pawar CD, Sarkate AP, Karnik KS, Shinde DB. Synthesis and evaluation of [N-(substituted phenyl)-2-(3-substituted) sulfamoyl) phenyl)] acetamide derivatives as anticancer agents. Egypt J Basic Appl Sci 2017;4:310-4.
6. Pomarnacka E, Kozlarska-Kedra I. Synthesis of 1-(6-chloro-1,1-dioxo-1,4,2-benzodithiazin-3-yl)semi-carbazides and their transformation into 4-chloro-2-mercapto-N-(4,5-dihydro-5-oxo-4-phenyl-1H-1,2,4-triazol-3-yl)benzenesulfonamides as potential anticancer and anti-HIV agents. Farmaco 2003;58:423-9.
7. Ghorab MM, Ragab FA, Hamed MM. Design, synthesis and anticancer evaluation of novel tetrahydroquinoline derivatives containing sulfonamide moiety. Eur J Med Chem 2009;44:4211-7.
8. Zayed MF, Ahmed HE, Ihmaid S, Omar AS, Abdelrahim AS. Synthesis and screening of some new fluorinated quinazolinone–sulphonamide hybrids as anticancer agents. J Taibah Univ Med Sci 2015;10:333-9.
9. Ou L, Han S, Ding W, Jia P, Yang B, Medina-Franco JL, et al. Parallel synthesis of novel antitumor agents: 1,2,3-triazoles bearing biologically active sulfonamide moiety and their 3D-QSAR. Mol Divers 2011;15:927-46.
10. Soyer Z, Uysal S, Parlar S, Tarikogullari Dogan AH, Alptuzun V. Synthesis and molecular docking studies of some 4-phthalimidobenzenesulfonamide derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors. J Enzyme Inhib Med Chem 2017;32:13-9.
11. Riaz S, Khan IU, Bajda M, Ashraf M, Qurat-Ul-Ain, Shaukat A, et al. Pyridine sulfonamide as a small key organic molecule for the potential treatment of Type-II diabetes mellitus and Alzheimer’s disease: In vitro studies against yeast ?-glucosidase, acetylcholinesterase and butyrylcholinesterase. Bioorg Chem 2015;63:64-71.
12. Ranjith PK, Pakkath R, Haridas KR, Kumari SN. Synthesis and characterization of new N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)amide/sulfonamide derivatives as possible antimicrobial and antitubercular agents. Eur J Med Chem 2014;71:354 65.
13. Gadad AK, Noolvi MN, Karpoormath RV. Synthesis and anti-tubercular activity of a series of 2-sulfonamido/trifluoromethyl-6-substituted imidazo[2,1-b]-1,3,4-thiadiazole derivatives. Bioorg Med Chem 2004;12:5651-9.
14. Singh K, Sharma PK. Synthesis, characterization and antimicrobial study of some benzenesulfonamide based bipyrazoles. Int J Pharm Pharm Sci 2014;6:345-51.
15. El-Gohary NS, Shaaban MI. Synthesis, antimicrobial, antiquorum-sensing, antitumor and cytotoxic activities of new series of fused [1, 3, 4] thiadiazoles. Eur J Med Chem 2013;63:185-95.
16. Abdel-Rahman SA, El-Gohary NS, El-Bendary ER, El-Ashry SM, Shaaban MI. Synthesis, antimicrobial, antiquorum-sensing, antitumor and cytotoxic activities of new series of cyclopenta(hepta)[b]thiophene and fused cyclohepta[b]thiophene analogs. Eur J Med Chem 2017;140:200-11.
17. Kamal A, Swapna P, Shetti RV, Shaik AB, Narasimha Rao MP, Gupta S, et al. Synthesis, biological evaluation of new oxazolidino-sulfonamides as potential antimicrobial agents. Eur J Med Chem 2013;62:661-9.
18. Kharbanda C, Alam MS, Hamid H, Javed K, Bano S, Dhulap A, et al. Synthesis and evaluation of pyrazolines bearing benzothiazole as anti-inflammatory agents. Bioorg Med Chem 2014;22:5804-12.
19. K?l?caslan S, Arslan M, Ruya Z, Bilen Ç, Ergün A, Gençer N, et al. Synthesis and evaluation of sulfonamide-bearing thiazole as carbonic anhydrase isoforms hCA I and hCA II. J Enzyme Inhib Med Chem 2016;31:1300-5.
20. Mishra CB, Kumari S, Angeli A, Monti SM, Buonanno M, Prakash A, et al. Design, synthesis and biological evaluation of N-(5-methyl-isoxazol-3-yl/1,3,4-thiadiazol-2-yl)-4-(3-substitutedphenylureido) benzenesulfonamides as human carbonic anhydrase isoenzymes I, II, VII and XII inhibitors. J Enzyme Inhib Med Chem 2016;31:174-9.
21. Gul HI, Kucukoglu K, Yamali C, Bilginer S, Yuca H, Ozturk I, et al. Synthesis of 4-(2-substituted hydrazinyl)benzenesulfonamides and their carbonic anhydrase inhibitory effects. J Enzyme Inhib Med Chem 2016;31:568-73.
22. Panday V. Modeling of carbonic anhydrase (II) inhibitory activities of sulphonilamide schiff bases by artificial neural network trained with different numerical techniques. Int J Pharm Pharm Sci 2018;10:202-7.
23. Siddiqui N, Pandeya SN, Khan SA, Stables J, Rana A, Alam M, et al. Synthesis and anticonvulsant activity of sulfonamide derivatives-hydrophobic domain. Bioorg Med Chem Lett 2007;17:255-9.
24. Patel TS, Vanparia SF, Patel UH, Dixit RB, Chudasama CJ, Patel BD, et al. Novel 2,3-disubstituted quinazoline-4(3H)-one molecules derived from amino acid linked sulphonamide as a potent malarial antifolates for DHFR inhibition. Eur J Med Chem 2017;129:251-65.
25. Fisher GM, Bua S, Del Prete S, Arnold MS, Capasso C, Supuran CT, et al. Investigating the antiplasmodial activity of primary sulfonamide compounds identified in open source malaria data. Int J Parasitol Drugs Drug Resist 2017;7:61-70.
26. Ugwu DI, Okoro UC, Ukoha PO, Okafor S, Ibezim A, Kumar NM, et al. Synthesis, characterization, molecular docking and in vitro antimalarial properties of new carboxamides bearing sulphonamide. Eur J Med Chem 2017;135:349-69.
27. Thakral S, Singh V. 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl]benzoic acid derivatives: In vitro antidiabetic activity, molecular modeling and in silico ADMET screening. Med Chem 2019;15:186-95.
28. Spooner DF, Sykes G. Laboratory assessment of antibacterial activity. In: Methods in Microbiology. Vol. 7. Ch. 4. London: Academic Press; 1972. p. 211-76.
29. Judge V, Narasimhan B, Ahuja M. Topological models for the prediction of antimycobacterial activity of 4-(5-substituted-1, 3, 4-oxadiazol-2-yl) pyridines. Med Chem Res 2012;21:1363-75.
30. Judge V, Narasimhan B, Ahuja M, Sriram D, Yogeeswari P, De Clercq E, et al. Synthesis, antimycobacterial, antiviral, antimicrobial activities, and QSAR studies of isonicotinic acid-1-(substituted phenyl)-ethylidene/cycloheptylidene hydrazides. Med Chem Res 2012;21:1935-52.
31. Trott O, Olson AJ. AutoDock vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010;31:455-61.
32. Ghorab MM, Soliman AM, Alsaid MS, Askar AA. Synthesis, antimicrobial activity and docking study of some novel 4-(4, 4-dimethyl-2, 6-dioxocyclohexylidene) methylamino derivatives carrying biologically active sulfonamide moiety. Arab J Chem 2017. DOI: 10.1016/j.arabjc.2017.05.022.
33. Zhao S, Wei P, Wu M, Zhang X, Zhao L, Jiang X, et al. Design, synthesis and evaluation of benzoheterocycle analogues as potent antifungal agents targeting CYP51. Bioorg Med Chem 2018;26:3242 53.
34. Szafra?ski K, S?awi?ski J, K?dzia A, Kwapisz E. Syntheses of novel 4-substituted N-(5-amino-1H-1,2,4-triazol-3-yl)pyridine-3-sulfonamide derivatives with potential antifungal activity. Molecules 2017;22:E1926.
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