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

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.

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.

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).

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