Naja oxiana venom-induced alkaline phosphatase (ALP) enzyme has been documented for its detrimental effects post envenomation in the victims. Therefore, the present study was designed to evaluate the effectiveness of 4-aminobenzenesulfonamide-based derivatives against cobra venom-induced ALP enzyme. Targeted derivatives were synthesized and characterized via FTIR, 1H NMR, and 13C NMR followed by docking targeted protein techniques. Furthermore, synthetic analogues were evaluated in vitro for their potential to halt ALP activity. Among all the synthetic compounds, (SB-5) showed remarkably potent inhibitory activity against the targeted enzyme (94%, IC50, 3.25 µM, p < 0.001). Furthermore, kinetic studies revealed that (SB-5) acts as a mixed-type inhibitor of ALP enzyme. Its Ki value (13.19 µM) indicated a high binding affinity, accompanied by a favorable safety profile - characterized by high gastrointestinal (GI) absorption, compliance with Lipinski's Rule of Five (0 violations), and a low likelihood of crossing the blood-brain barrier, suggesting good oral bioavailability. The Ramachandran plot offered further insight into the positioning of amino acid residues within the most favored regions, thereby reinforcing the potential to inhibit ALP activity. The present study confirms the effectiveness of 4-aminobenzenesulfonamide-based derivative (SB-5) as a promising inhibitor of ALP and as a lead candidate for future drug development.
Khan et al. (Fri,) studied this question.
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