Antimicrobial Activity Studies of 3-Substituted Indole-2-one and -thione derivatives and Molecular Docking and ADME Evaluations

Yıl 2023, Cilt: 6 Sayı: 1, 13 - 26, 01.07.2023

Derya Doğanay Şevval Maral Özcan Aykol Ahmet Mesut Şentürk Süreyya Ölgen

https://doi.org/10.54994/emujpharmsci.1202754

Öz

Increasing antibiotic resistance is an important problem for public health therefore new antimicrobial compounds are needed. In this study, the antimicrobial effects of 3-Substituted Indole-2-one and -thione derivatives were investigated. Antimicrobial effects of previously synthesized 18 different 3-substituted indole-2-one and 2-thione derivatives against 5 different microorganisms were investigated and the structure-activity relationships and drug-like properties of compounds were analyzed by molecular docking and in silico prediction studies. The in vitro antimicrobial activities of compounds were tested by microdilution method. The most active compounds were found as 2, 3, 4, 5, 6, 7, 8 at 125 μg/mL of MIC value. Compounds 2 and 3 were found to be active against S. enterica and compounds 4, 5, 6, 7, and 8 were found to be active against methicillin-resistant S. aureus. According to molecular docking studies, all compounds presented weaker binding properties than ciprofloxacin, ampicillin and gentamicin. The predicted values for molecular weight, log P, PSA, crossing the BBB, GI absorption properties and type of CYPP450 inhibition data of compounds were found promising for drug-like properties. 3-Substituted Indole-2-one and -thione derivatives can proivide an important contribution to develop alternative antimicrobial agents.

Anahtar Kelimeler

Antimicrobial activity, Minimum inhibitory concentration, Molecular docking, Structure-activity relationship, 3-Substituted-indole-2-on and 2-thione

Destekleyen Kurum

-

Proje Numarası

-

Teşekkür

-

Kaynakça

• Banerjee D, Yogeeswari P, Bhat P, Thomas A, Srividya M, Sriram D (2011). Novel isatinyl thiosemicarbazones derivatives as potential molecule to combat HIV-TB co-infection. Eur J Med Chem 46(1): 106-121.
• Bhaskar G, Arun Y, Balachandran C, Saikumar C, Perumal PT (2012). Synthesis of novel spirooxindole derivatives by one pot multicomponent reaction and their antimicrobial activity. Eur J Med Chem 51: 79-91.
• Chodvadiya VD, Pambhar KD, Parmar ND, Dhamsaniya AP, Chhatbar PV, Ram HN, Patel PK (2019). Synthesis and characterization of N-methyl indole derivatives via desulfitative displacement by various amines and Its antimicrobial activity. World Sci. News 120(2): 181-191.
• Clinical and Laboratory Standards Institute (2018). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that GrowAerobically, Approved Standard. seventh ed. Wayne: CLSI.
• Doganay D, Ozcan MS, Senturk MA, Olgen S (2022). Antimicrobial Evaluation, Molecular Docking and ADME Properties of Indole Amide Derivatives. Lett Drug Des Discov 19(5): 387-396.
• Hussain AZ, Meeran MN, Sankar A (2016). Synthesis, characterization and antimicrobialactivityof spiro-4-thiazolidione derivativesfrom 5-substituted indole-2,3-dione. Pharma Chemica 8(2): 292-296.
• Kang MS, Choi EK, Choi DH, Ryu SY, Kang IC (2008). Antibacterial activity of pyrrolidine dithiocarbamate. Fems microbiol Lett 280 (2): 250-254.
• Karimi AR, Dalirnasab Z, Yousefi GH, Akbarizadeh AR (2015). Synthesis of mono and bis-[3,3-di(indolyl)indolin-2-ones] and evaluation of their antimicrobial activity. Res Chem Intermed 41(12): 10007-10016.
• Khan FA, Maalik A (2015). Advances in Pharmacology of Isatin and its Derivatives: A Review. Tropical J Pharm Res 14(10): 1937-1942.
• Konstantinović SS, Kapor A, Radovanović BC, Deak A (2008). Synthesis, X-ray and antimicrobial activity of isatin-3- phenylhydrazone. Chem Ind Chem Eng Quart 14(1): 27-34.
• Kumar RS, Rajesh SM, Perumal S, Banerjee D, Yogeeswari P, Sriram D (2010). Novel three-component domino reactions of ketones, isatin and amino acids: synthesis and discovery of antimycobacterial activity of highly functionalised novel dispiropyrrolidines. Eur J Med Chem 45(1): 411-422.
• Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2012). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced drug delivery reviews, 64, 4-17.
• Mendoza-Figueroa HL, Serrano-Alva MT, Aparicio-Ozores G, Martínez-Gudiño G, Suárez-Castillo OR, Pérez-Rojas NA, Morales-Ríos MS (2018). Synthesis, antimicrobial activity, and molecular docking study of fluorine-substituted indole-based imidazolines. Med Chem Res; 27(6): 1624-1633.
• Mohanan K, Sindhu K, Rijulal G (2008). Microwave assisted synthesis, spectroscopic, thermal, and antifungal studies of some lanthanide(III) complexes with a heterocyclic bishydrazone. J Rare Earths 26(1): 16-21.
• Nandakumar A, Thirumurugan P, Perumal PT, Vembu P, Ponnuswamy MN, Ramesh P (2010). One-pot multicomponent synthesis and anti-microbial evaluation of 2'-(indol-3-yl)-2-oxospiro(indoline-3,4'-pyran) derivatives. Bioorg Med Chem Lett 20(14): 4252- 4258.
• Olgen S, Akaho E, Nebioglu D (2005). Synthesis and anti-tyrosine kinase activity of 3-(substituted-benzylidene)-1,3-dihydro-indolin derivatives: investigation of their role against Src receptor tyrosine kinase with the application of receptor docking studies. Il Farmaco; 60(7): 497-506.
• Olgen S, Ozkan S (2009). A study of 3-substituted benzylidene-1, 3-dihydro-indoline derivatives as antimicrobial and antiviral agents. Z Naturforsch C 64(3): 155-162.
• Pandeya SN, Singh BN, Shukla SK, Singh M (2008). Synthesis and antimicrobial activity of N-norfloxacin Mannich basis of isatin and its derivatives. Asian J Chem 20(7): 5377-5382.
• Piscopo E, Diurno MV, Gagliardi R, Cucciniello M, Veneruso G (1987). Studies on heterocyclic compounds: indole-2,3-dione derivatives. VII. Variously substituted hydrazones with antimicrobial activity. Boll Soc Ital Biol Sper 63(9): 827-832.
• Piscopo E, Diurno MV, Imperadrice F, Caliendo V, Nebulosi R (1986). Studies on heterocyclic compounds: indole-2,3-dione derivatives. VI. 3-Aryliminoindole-2(3H)-ones and their Mannich bases with antimicrobial activity. Boll Soc Ital Biol Sper 62(12): 1449-1455.
• Piscopo E, Diurno MV, Imperadrice F, Cucciniello M, Veneruso G (1986). Studies on heterocyclic compounds: indole-2,3-dione derivatives. V. Structure-antimicrobial activity of aromatic and heterocyclic azomethines of indole- and substituted indole-2,3-diones. . Boll Soc Ital Biol Sper 62(12): 1441-1447.
• Sanli-Yurudu NO, Kimiran-Erdem A, Arslan-Aydogdu EO., Zeybek Z, Gurun S (2012). Efficacy of colloidal silver-hydrogen peroxide and 2-Bromo-2-nitroporopane-1, 3-diol compounds against different serogroups of Legionella pneumophila Strains. Indian J Microbiol 52(1): 54-59.
• Shaker AM, Abdelall EK, Abdellatif KR, Abdel-Rahman HM (2020). Synthesis and biological evaluation of 2-(4-methylsulfonyl phenyl) indole derivatives: Multi-target compounds with dual antimicrobial and anti-inflammatory activities. BMC chemistry 14(1): 1-15.
• Shirinzadeh H, Süzen S, Altanlar N, Westwell AD (2018). Antimicrobial activities of new indole derivatives containing 1, 2, 4-triazole, 1, 3, 4-thiadiazole and carbothioamide. Turk J Pharm Sci. 15(3): 291.
• Singh UK, Pandeya SN, Jindal S, Pandey M., Srivastava BK, Singh A (2010). Synthesis and antimicrobialactivity of Schiff's and Mannich bases of 1H-indole-2,3-dione derivatives. Pharma chem 2(2): 392-399.
• Sudha RK, Kandula P, Anupama B, Chenchu L (2015). In vitro evaluation of some novel 5,5-disubstituted-1,2,4-triazolidine-3-one derivatives. International J Pharm and Life Sci 6(4): 4417-4426.
• Swiss ADMET Prediction, Swiss Institute of Bioinformatics, Switzerland, Available from: http://swissadme.ch/