Synthesis, crystal structure, anticancer and molecular docking studies of quinolinone-thiazolidinone hybrid molecules

Kumar, Vasantha; Rai, Vaishali; Udupi, Vishwanatha; Naveen, S.; Pai, Vidya; Krishnappagowda, Lokanath Neratur; Poojary, Boja

doi:10.1007/s13738-021-02342-5

Cited by 10 publications

(8 citation statements)

References 47 publications

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“…[26] Its introduction in the moiety often increases metabolic stability, increases lipophilicity and also increases binding affinity to the target protein. [27] Inspired by the very remarkable antimicrobial activity of thiazolidinone class of heterocycles, importance of fluorine in medicinal application and in continuation of our work on fluorinated molecules, [28,29] thiazole and thiazolidinone derivatives, [30][31][32][33] in the present work we synthesized fluorinated thiazolidinone derivatives having different aryl/heteroaryl substitutions at 5 th position and explored their antibacterial activity against different gram + ve and gram À ve bacterial strains. Most potent compounds were then screened against clinical isolates of MRSA.…”

Section: Introductionmentioning

confidence: 99%

Potential Fluorinated Anti‐MRSA Thiazolidinone Derivatives with Antibacterial, Antitubercular Activity and Molecular Docking Studies

Poojary

Kumar

Premalatha³

et al. 2022

Chemistry & Biodiversity

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MRSA infection is one of the alarming diseases in the current scenario. Identifying newer molecules to treat MRSA infection is of urgent need. In the present study, we have designed fluorinated thiazolidinone derivatives with various aryl/heteroaryl units at 5 th position of the thiazolidinone core as promising anti-MRSA agents. All the compounds were screened for antibacterial activity against four bacterial strains. Among the tested compounds, the halogenated compounds with simple arylidene ring, (5Z 4f) and (5Z)-5-[(3,5-difluorophenyl)methylidene]-2-[(1,3-thiazol-2-yl)amino]-1,3thiazol-4(5H)-one (4g) showed excellent activity with MIC 3.125 -6.25 μg/mL against S. aureus and P. aeruginosa organism. Furthermore, these potent compounds were screened against MRSA strains, ESKAPE panel organism, and H37Rv mycobacterium strain. Compounds 4c (MIC 0.39 μg/mL), and 4f (MIC 0.39 and 0.79 μg/mL) displayed promising activity against MRSA strains (ATCC and clinical isolates, respectively). The most potent compounds, 4c and 4f eradicated the growth of bacterial colonies in a time-kill assay indicated that these are bactericidal in nature. The preliminary toxicity study of the potent molecules revealed that these compounds are non-hemolytic in nature as they did not induce lysis in human RBCs. In addition, the molecular docking and dynamics studies of compounds 4b, 4c, 4f and 4g were carried out on MurB protein of S. aureus (PDB code: 1HSK). Docking results demonstrated remarkable hydrogen bonding interaction with key amino acids ARG310, ASN83, GLY79 and π-π interactions with TYR149 which confirm the mode of action of the molecules.

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Section: Introductionmentioning

confidence: 99%

Potential Fluorinated Anti‐MRSA Thiazolidinone Derivatives with Antibacterial, Antitubercular Activity and Molecular Docking Studies

Poojary

Kumar

Premalatha³

et al. 2022

Chemistry & Biodiversity

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“…On the basis of the pharmacological profile of thiazolidinone and pyrazole, and in continuation of our work on antidiabetic-, [35,38] thiazolidinone-, [39][40][41] and pyrazole [42,43] based compounds, it was worth combining two scaffolds to construct some fluorinated hybrid molecules to enhance the biological activities. In this view, different fluorinated 2,3-disubstituted thiazolidin-4-ones were clubbed with various 3-(aryl/ benzyloxyaryl)-pyrazole-4-carbaldehydes and evaluated for their αamylase inhibitory and antioxidant activities.…”

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confidence: 99%

In vitro and in silico studies of fluorinated 2,3‐disubstituted thiazolidinone‐pyrazoles as potential α‐amylase inhibitors and antioxidant agents

Ganavi

Ramu

Kumar

et al. 2021

Archiv der Pharmazie

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As part of our effort to identify potent α-amylase inhibitors, in the present study, a novel series of fluorinated thiazolidinone-pyrazole hybrid molecules were prepared by the condensation of 3-(aryl/benzyloxyaryl)-pyrazole-4-carbaldehydes with fluorinated 2,3disubstituted thiazolidin-4-ones. The structures of the newly synthesized compounds were confirmed by infrared, 1 H nuclear magnetic resonance (NMR), 13 C NMR, and liquid chromatography-mass spectrometry data. All the compounds were screened for their αamylase inhibitory and free radical scavenging activities by DPPH (1,1-diphenyl-2picrylhydrazyl) and ABTS methods. Among the tested compounds, compound 8g emerged as a promising α-amylase inhibitor with IC 50 = 0.76 ± 1.23 µM, and it was found to be more potent than the standard drug acarbose (IC 50 = 0.86 ± 0.81 μM). Compounds 8b and 8g showed strong free radical scavenging activity compared to the standard butylated hydroxyl anisole. The kinetic study of compound 8g revealed the reversible, classical competitive inhibition mode on the α-amylase enzyme. Molecular docking and dynamic simulations studies were performed for the most potent compound 8g, which displayed remarkable hydrogen bonding with the α-amylase protein (PDB ID: 1DHK).

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“…Heterocycle-fused quinolinone is another privileged structure used as a building block in drug discovery. The quinolinone hybrids have shown biological activities, including antimicrobial [ 75 ], anti-inflammatory [ 76 ], anticancer [ 77 ], anti-Alzheimer [ 78 ], and anti-leishmanial [ 79 ] effects. Interestingly, quinolinone derivatives can successfully inhibit IDH1 mutants R132H, R132C, R132G, and R132L and display good selectivity vs. the wild-type IDH protein [ 80 ].…”

Section: Quinolinone Hybridsmentioning

confidence: 99%

A Review of the Recent Developments of Molecular Hybrids Targeting Tubulin Polymerization

Ebenezer

Shapi

Tuszyński

2022

IJMS

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Microtubules are cylindrical protein polymers formed from αβ-tubulin heterodimers in the cytoplasm of eukaryotic cells. Microtubule disturbance may cause cell cycle arrest in the G2/M phase, and anomalous mitotic spindles will form. Microtubules are an important target for cancer drug action because of their critical role in mitosis. Several microtubule-targeting agents with vast therapeutic advantages have been developed, but they often lead to multidrug resistance and adverse side effects. Thus, single-target therapy has drawbacks in the effective control of tubulin polymerization. Molecular hybridization, based on the amalgamation of two or more pharmacophores of bioactive conjugates to engender a single molecular structure with enhanced pharmacokinetics and biological activity, compared to their parent molecules, has recently become a promising approach in drug development. The practical application of combined active scaffolds targeting tubulin polymerization inhibitors has been corroborated in the past few years. Meanwhile, different designs and syntheses of novel anti-tubulin hybrids have been broadly studied, illustrated, and detailed in the literature. This review describes various molecular hybrids with their reported structural–activity relationships (SARs) where it is possible in an effort to generate efficacious tubulin polymerization inhibitors. The aim is to create a platform on which new active scaffolds can be modeled for improved tubulin polymerization inhibitory potency and hence, the development of new therapeutic agents against cancer.

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Synthesis, crystal structure, anticancer and molecular docking studies of quinolinone-thiazolidinone hybrid molecules

Cited by 10 publications

References 47 publications

Potential Fluorinated Anti‐MRSA Thiazolidinone Derivatives with Antibacterial, Antitubercular Activity and Molecular Docking Studies

Potential Fluorinated Anti‐MRSA Thiazolidinone Derivatives with Antibacterial, Antitubercular Activity and Molecular Docking Studies

In vitro and in silico studies of fluorinated 2,3‐disubstituted thiazolidinone‐pyrazoles as potential α‐amylase inhibitors and antioxidant agents

A Review of the Recent Developments of Molecular Hybrids Targeting Tubulin Polymerization

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