ANTIMICROBIAL AND IN SILICO ADMET SCREENING OF NOVEL (E)-N-(2-(1H-INDOL-3-YL-AMINO) VINYL)-3-(1-METHYL-1H-INDOL-3-YL)-3-PHENYLPROPANAMIDE DERIVATIVES
Keywords:Antimicrobial, ADMET, Phenylpropanamide, Nil, Indole and Nitro methane
Objective: Synthesis, in silico absorption, distribution, metabolism, excretion, toxicity (ADMET) and in vitro antimicrobial screening of (E)-N-(2-(1H-indol-3-ylamino) vinyl)-3-(1-methyl-1H-indol-3-yl)-3-phenylpropanamide derivatives.
Methods: (E)-N-(2-(1H-indol-3-ylamino)Â vinyl)-3-(1-methyl-1H-indol-3-yl)-3Â phenylpropane-amide derivatives were synthesized by combining indole ethanolamine and substituted Meldrum's adduct. The synthesized compounds were subjected to in vitro antimicrobial study by cup plate method and in silico ADMET properties using ACD/I-Lab 2.0.
Results: The in vitro antimicrobial screening against precarious pathogenic microorganisms viz, Pseudomonas aureginosa, Staphylococcus aureus, Escherichia coli, Vibrio cholerae, and the antifungal activity against Candida albicans, Aspergillus niger, Penicillin chrysogenum and Cladosporium oxysporum strains. The results revealed that compounds 5b, 5c, 5d and 5e showed good antimicrobial property and obeyed the in silico pharmacokinetic parameters.
Conclusion: The encouraging results exhibited by the compounds (E)-N-(2-(1H-indol-3-ylamino) vinyl)-3-(1-methyl-1H-indol-3-yl)-3-phenyl propanamide derivatives, 5(a-e) can be explored as possible hits in antimicrobial therapy. The molecules obey the Lipinski rule of five when tested in silico and can be used in understanding the quantitative structure-activity relationship (QSAR) parameters.
Mehta DS, Sikotra KH, Shah VH. Synthesis and biological screening of some novel indole derivatives. Indian J Chem 2005; 44B:2590-7.
Whitehead CW, Whitesitt AA. Effects of lipophilic substituents on some biological properties of indoles. J Med Chem 1974;17:1298-304.
Malesani G, Chiarelotto G, Dallacqua F, Vedali D. Antimicrobial properties of some 3-acyl-4, 7-disubstituted indoles. Farmaco 1975;30:137-46.
Donawade DS, Gadaginamath GS. Some electrophilic substitution reactions on 1-substituted-3-acetyl/carbethoxy-5-hydroxy-2-methylindole and antimicrobial activity of these new indole derivatives. Indian J Chem 2005;44B:1679-85.
Tsotinis A, Varvaresou A, Calogeropoulou T, Siatra-Papastaikoudi T, Tiligada A. Synthesis and antimicrobial evaluation of indole containing derivatives of 1,3,4-triazole and their open-chain counterparts. Arzneim-Forsch/Drug Res 1997;47:307-10.
Cooper LC, Chicchi GG, Dinnell K, Elliott JM, Hollingworth GJ, Kurtz MM, et al. 2-Aryl Indole Nk1 receptor antagonists: optimization of indole substitution. Bioorg Med Chem Lett 2001;11:1233-6.
Andrew MT, David WF, Alan JK, William AD. Synthesis of 2,2â€™-dithiobis(1H-indole-3-alkanamides) and investigation of their inhibitory activity against epidermal growth factor receptor and pp600-src protein tyrosine kinases. J Med Chem 1994;37:598-609.
Francis G, Pascal M, Delphine C, Michael S, FranÃ§ois L, Muriel D. Synthesis of N-aryl-3-(indol-3-yl)propanamides and their immunosuppressive activities. Bioorg Med Chem Lett 2010; 20:5203-6.
Jacobs RT, Brown FJ, Cronk LA, Aharony D, Buckner CK, Kusner EJ, et al. Substituted 3-(phenylmethyl)-1H-indole-5-carboxa-mides and 1-(phenylmethyl)indole-6-carboxamides as potent, selective, orally active antagonists of the peptidoleukotrienes. J Med Chem 1993;36:394-409.
Duflos M, Nourrsson MR, Brelet J, Courant J, LeBaut B, Brimaud N, et al. N-Pyridinyl-indole-3-(alkyl)carboxamides and derivatives as potential systemic and topical inflammation inhibitors. Eur J Med Chem 2001;36:545-53.
Dardennes E, Gerard S, Petermann C, Sapi J. Diastereoselective trimolecular condensation between indole, Meldrumâ€™s acid and chiral sugar-derived aldehydes. Tetrahedron Asymmetry 2010;21:208-15.
Dardennes E, Kulyassa AK, Boisbrun M, Petermann C, Laronze JY, Sapi J. Diastereocontrolled multicomponent pathway to 3,4-heterocycle-annulated tetrahydro-carbolines. Tetrahedron Asymmetry 2005;16:1329-39.
Cochard F, Laronze M, Sigaut P, Sapi J, Laronze JY. Synthesis of carbazoles by a lanced four component condensation. Tetrahedron Lett 2004;45:1703-7.
Siddalingamurthy E, Mahadevan KM, Shrungesh Kumar TO. Choline chloride/Urea ionic liquid catalyzed a convenient one-pot synthesis of indole-3-propanamide derivatives. Synth Commun 2013;43:3153-62.
Saundane AR, Rudresh K, Satyanarayan ND, Hiremath SP. Pharmacological screening of 6H, 11H-indole[3,2-c]isoquinolin-5-ones and their derivatives. Indian J Pharm Sci 1998;6:379-83.
Laxmi S, Ankit J, Upendra B. Synthesis and antimicrobial activity of some novel schiff base derivatives of 5-nitro isatin. Asian J Pharm Life Sci 2011;1 Suppl 3:2231-4423.
Bhovi MG, Gadaginamath GS. 1, 3-Dipolar cycloaddition reactions: Synthesis and antimicrobial activity of novel 1-triazolylindole and 1-triazolylbenz-[g]indole derivatives. Indian J Chem 2005;44B:1068-73.
Feixiong C, Weihua L, Yadi Z, Jie S, Zengrui W, Guixia L, et al. Admetsar: a comprehensive source and free tool for assessment of chemical ADMET properties. J Chem Inf Model 2012;52:3099-105.
Jagadeesh NM, Mahadevan KM, Kumara MN, Prashantha N. Synthesis and molecular docking study of N-alkyl/aryl-2-aryl indol-3-yl glyoxylamides as novel anticancer agents. Int J Pharm Pharm Sci 2014;6:921-6.
Manjunatha KS, Manjulatha K, Satyanarayan ND, Kaviraj MY, Adarsha HJ. Anti-proliferative and ADMET screening of novel 3-(1H-indol-3-yl)-1, 3-diphenylpropan-1-one derivatives. Cogent Chem 2016;2:1-11.
Lin JH, Yamazaki M. Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin Pharmacokinet 2003;42:59-98.
David L, Olivier S, HervÃ© G, Maria AM, Bruno OV. FAF-drugs 2: free ADME/tox filtering tool to assist drug discovery and chemical biology projects. BMC Bioinf 2008;9:396.
Siddalingamurthy E, Mahadevan KM, Jagadeesh NM, Kumara MN. Synthesis and docking study of 3-(N-alkyl/aryl piperidyl) indoles with serotonin-5HT, H1 and CCR2 antihistamine receptors. Int J Pharm Pharm Sci 2014;6:475-82.
Olgena S, Altanlarb N, KarataylÄ±c E, BozdayÄ±c M. Antimicrobial and antiviral screening of novel indole carboxamide and propanamide derivatives Z. Naturforsch 2008;63c:189-95.