Facile Synthesis, Antimicrobial Activity, and Molecular Docking Analysis of 8-hydroxyquinoline-4-thiazolidinone Hybrids

Overview

Journal Future Med Chem

Specialties Chemistry
Pharmacy

Date 2025 Feb 14

PMID 39949271

Authors

Jagruti Peddapaka

Aayesha Nasreen

Tulja Sanam

Mahammad Ghouse Shaik

Baijayantimala Swain

Shweta Sanwer

Ravi Alvala

Mohammed Arifuddin

Sridhar Goud Nerella

Affiliations

Soon will be listed here.

Abstract

Background: 8-Hydroxyquinoline and 4-thiazolidinone derivatives are promising antimicrobial agents, recognized for their activity against resistant pathogens.

Aim: The aim of this study is to develop 8-hydroxyquinoline-4-thiazolidinone derivatives as potential antimicrobial agents.

Methods: Using a one-pot reaction with sodium tetrafluoroborate as an efficient and eco-friendly catalyst, compounds 6a - l were synthesized and subsequently screened for antibacterial and antifungal activity. Additionally, molecular docking and molecular dynamic simulations were performed to evaluate the active compounds and gain deeper insights into their potential as antimicrobial agents.

Results: Compounds 6f and 6 g showed superior antibacterial activity to ciprofloxacin, particularly against Gram-negative bacteria, while 6b, 6 g, and 6 h demonstrated strong antifungal effects. Molecular docking, molecular dynamics simulations, and MM-GBSA calculations highlighted strong binding interactions and stable conformations of the active compounds within binding pocket of the FabZ enzyme. The ADMET analyses further indicated that these compounds possess favorable drug-like properties.

Conclusion: The synthesized 8-hydroxyquinoline-4-thiazolidinone hybrids exhibit strong potential as broad-spectrum antimicrobial agents and merit further investigation as drug candidates.

References

Nwobodo D, Ugwu M, Oliseloke Anie C, Al-Ouqaili M, Ikem J, Victor Chigozie U . Antibiotic resistance: The challenges and some emerging strategies for tackling a global menace. J Clin Lab Anal. 2022; 36(9):e24655. PMC: 9459344. DOI: 10.1002/jcla.24655. View

Forli S, Huey R, Pique M, Sanner M, Goodsell D, Olson A . Computational protein-ligand docking and virtual drug screening with the AutoDock suite. Nat Protoc. 2016; 11(5):905-19. PMC: 4868550. DOI: 10.1038/nprot.2016.051. View

Gajic I, Kabic J, Kekic D, Jovicevic M, Milenkovic M, Culafic D . Antimicrobial Susceptibility Testing: A Comprehensive Review of Currently Used Methods. Antibiotics (Basel). 2022; 11(4). PMC: 9024665. DOI: 10.3390/antibiotics11040427. View

Chan S, Chui C, Chan S, Kok S, Chan D, Tsoi M . Synthesis of 8-hydroxyquinoline derivatives as novel antitumor agents. ACS Med Chem Lett. 2014; 4(2):170-4. PMC: 4027363. DOI: 10.1021/ml300238z. View

Goud N, Ghouse M, Nagaraju C, Bharath R, Alvala M, Kumar P . Automated Radiosynthesis and Molecular Docking Studies of Coumarin- Triazole Hybrid with fluorine-18: A feasibility study. Curr Radiopharm. 2021; 15(1):40-49. DOI: 10.2174/1874471014666210129141221. View

Joaquim A, Gionbelli M, Gosmann G, Fuentefria A, Lopes M, de Andrade S . Novel Antimicrobial 8-Hydroxyquinoline-Based Agents: Current Development, Structure-Activity Relationships, and Perspectives. J Med Chem. 2021; 64(22):16349-16379. DOI: 10.1021/acs.jmedchem.1c01318. View

Rbaa M, Jabli S, Lakhrissi Y, Ouhssine M, Almalki F, Hadda T . Synthesis, antibacterial properties and bioinformatics computational analyses of novel 8-hydroxyquinoline derivatives. Heliyon. 2019; 5(10):e02689. PMC: 6820249. DOI: 10.1016/j.heliyon.2019.e02689. View

Domalaon R, Idowu T, Zhanel G, Schweizer F . Antibiotic Hybrids: the Next Generation of Agents and Adjuvants against Gram-Negative Pathogens?. Clin Microbiol Rev. 2018; 31(2). PMC: 5967690. DOI: 10.1128/CMR.00077-17. View

Prachayasittikul V, Prachayasittikul S, Ruchirawat S, Prachayasittikul V . 8-Hydroxyquinolines: a review of their metal chelating properties and medicinal applications. Drug Des Devel Ther. 2013; 7:1157-78. PMC: 3793592. DOI: 10.2147/DDDT.S49763. View

10.

Trotsko N . Antitubercular properties of thiazolidin-4-ones - A review. Eur J Med Chem. 2021; 215:113266. DOI: 10.1016/j.ejmech.2021.113266. View

11.

Salam M, Al-Amin M, Salam M, Pawar J, Akhter N, Rabaan A . Antimicrobial Resistance: A Growing Serious Threat for Global Public Health. Healthcare (Basel). 2023; 11(13). PMC: 10340576. DOI: 10.3390/healthcare11131946. View

12.

. Global burden of bacterial antimicrobial resistance 1990-2021: a systematic analysis with forecasts to 2050. Lancet. 2024; 404(10459):1199-1226. PMC: 11718157. DOI: 10.1016/S0140-6736(24)01867-1. View

13.

Cascioferro S, Parrino B, Carbone D, Schillaci D, Giovannetti E, Cirrincione G . Thiazoles, Their Benzofused Systems, and Thiazolidinone Derivatives: Versatile and Promising Tools to Combat Antibiotic Resistance. J Med Chem. 2020; 63(15):7923-7956. PMC: 7997583. DOI: 10.1021/acs.jmedchem.9b01245. View

14.

Nerella S, Alvala R, Kalle A, Alvala M . Design and synthesis of novel coumarin-benzimidazole hybrids as human galectin-1 inhibitors. Future Med Chem. 2024; 16(9):843-857. PMC: 11188815. DOI: 10.4155/fmc-2023-0273. View

15.

Bhat S, Jagruthi P, Srinivas A, Arifuddin M, Qureshi I . Synthesis and characterization of quinoline-carbaldehyde derivatives as novel inhibitors for leishmanial methionine aminopeptidase 1. Eur J Med Chem. 2019; 186:111860. DOI: 10.1016/j.ejmech.2019.111860. View

16.

Zhu M, Tse M, Weller J, Chen J, Blainey P . The future of antibiotics begins with discovering new combinations. Ann N Y Acad Sci. 2021; 1496(1):82-96. PMC: 8290516. DOI: 10.1111/nyas.14649. View

17.

Singh P, Goud N, Swain B, Sahoo S, Choli A, Angeli A . Synthesis of a new series of quinoline/pyridine indole-3-sulfonamide hybrids as selective carbonic anhydrase IX inhibitors. Bioorg Med Chem Lett. 2022; 70:128809. DOI: 10.1016/j.bmcl.2022.128809. View

18.

Prestinaci F, Pezzotti P, Pantosti A . Antimicrobial resistance: a global multifaceted phenomenon. Pathog Glob Health. 2015; 109(7):309-18. PMC: 4768623. DOI: 10.1179/2047773215Y.0000000030. View

19.

Kaur Manjal S, Kaur R, Bhatia R, Kumar K, Singh V, Shankar R . Synthetic and medicinal perspective of thiazolidinones: A review. Bioorg Chem. 2017; 75:406-423. DOI: 10.1016/j.bioorg.2017.10.014. View

20.

Rossi R, Ciofalo M . An Updated Review on the Synthesis and Antibacterial Activity of Molecular Hybrids and Conjugates Bearing Imidazole Moiety. Molecules. 2020; 25(21). PMC: 7663458. DOI: 10.3390/molecules25215133. View