Synthesis, characterization, in-silico, and in-vitro evaluation of 4-amino-N-(4-aminophenyl)benzene sulfonamide derivatives against Naja oxiana 5'-nucleotidases (5'-NT) enzyme.

AIM: 5'-Nucleotidase (5'-NT) enzyme has been reported for its detrimental effects post-Naja oxiana (N. oxiana) envenomation via generation of adenosine moiety. Therefore, the present study was designed to evaluate anti-5'-NT potentials of various 4-amino-N-(4-aminophenyl)benzene sulfonamide derivatives (HAS-series).

METHODS

Targeted compounds were studied computationally and subsequently synthesized and analyzed with different spectroscopic techniques. Furthermore, these analogues were evaluated in vitro for their potentials to halt 5'-NT activity.

RESULTS

Among the 10 newly synthesized compounds, HAS-1 (IC50 = 12 ng/mL, 99% effective) and HAS-2 (IC50 = 18 ng/mL, 96% effective) showed remarkable potentials (p > 0.5) when compared with standard antidote having low binding energies (-8.1 kcal/mol and -7.5 kcal/mol) against the target. Favorable pharmacokinetic safety profile was observed characterized with high absorption, compliance in Lipinski's rule, low penetration power to the brain with effective bioavailability.

CONCLUSIONS

Based on the data compiled, both potential analogues could be promising target against 5'-NT to cope with adenosine-induced toxicities. However, detailed study is inevitable to access their lipophilicity and toxicity profile prior safely use in the victims.