Abstract
AIM: Cobra venom phospholipase A(2) (PLA(2)) 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 PLA(2) enzyme. METHODS: Amide and sulfonamide thiazole derivatives were synthesized and characterized using FTIR, (1)HNMR and (13)CNMR followed by docking targeted protein techniques. Furthermore, synthetic analogues were evaluated in vitro for their potentials to neutralize PLA(2) 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; IC(50) = 1 nM) to mask cent percent PLA(2) activity. Moreover, Ramachandran plot further conferred about the location of amino acid residues in the most favored region and, therefore, attributed to confiscate PLA(2) 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 PLA(2) inhibitor to reverse PLA(2)-induced snake venom poisoning in future.