Future medicinal chemistry · 2025
Design, synthesis, and molecular docking studies of thiazole derivatives against phospholipase A2 (Naja oxiana) venom.
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Nayyab Bibi F, Shah Muhammad, Asad Muhammad H H B, Zaidi Asma, Alam Fiaz, Mannan Abdul, Rashid Umer
Аннотация
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.
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.