Design, synthesis, and molecular docking studies of thiazole derivatives against phospholipase A₂ (Naja oxiana) venom.

IF 3.2 4区医学 Q3 CHEMISTRY, MEDICINAL

Future medicinal chemistry Pub Date : 2025-03-01 Epub Date: 2025-03-17 DOI:10.1080/17568919.2025.2478807

Bibi F Nayyab, Muhammad Shah, Muhammad H H B Asad, Asma Zaidi, Fiaz Alam, Abdul Mannan, Umer Rashid

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引用次数: 0

Abstract

Aim: Cobra venom phospholipase A₂ (PLA₂) has been known to induce life threatening effects post-envenomation in the victims. Being the most abundant and noxious component of snake venom, present study was envisaged to investigate new drug candidates against PLA₂ enzyme.

Methods: Amide and sulfonamide thiazole derivatives were synthesized and characterized using FTIR, ¹HNMR and ¹³CNMR followed by docking targeted protein techniques. Furthermore, synthetic analogues were evaluated in vitro for their potentials to neutralize PLA₂ activity.

Results: Among the pool of synthetic derivatives, compound (7) (ethyl 2-(2-(4-isobutylphenyl)propanamido)thiazole-4-carboxylate) was found to be completely effective (p > 0.05; IC₅₀ = 1 nM) to mask cent percent PLA₂ activity. Moreover, Ramachandran plot further conferred about the location of amino acid residues in the most favored region and, therefore, attributed to confiscate PLA₂ activity. Furthermore, ADME profile suggested that compound (7) possesses systemic bioavailability and efficacy with favorable safety profile (high solubility, membrane permeability, metabolic stability, and low potential for off-target results).

Conclusion: Present study highlighted compound (7) as a potential PLA₂ inhibitor to reverse PLA₂-induced snake venom poisoning in future.

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来源期刊

Future medicinal chemistry CHEMISTRY, MEDICINAL-

CiteScore

5.80

自引率

2.40%

发文量

118

审稿时长

4-8 weeks

期刊介绍： Future Medicinal Chemistry offers a forum for the rapid publication of original research and critical reviews of the latest milestones in the field. Strong emphasis is placed on ensuring that the journal stimulates awareness of issues that are anticipated to play an increasingly central role in influencing the future direction of pharmaceutical chemistry. Where relevant, contributions are also actively encouraged on areas as diverse as biotechnology, enzymology, green chemistry, genomics, immunology, materials science, neglected diseases and orphan drugs, pharmacogenomics, proteomics and toxicology.