Anti-alkaline phosphatases (ALP) potentials of potent 4-aminobenzenesulfonamide derivatives against Naja oxiana venom.

IF 3.4 4区医学 Q3 CHEMISTRY, MEDICINAL

Future medicinal chemistry Pub Date : 2025-09-19 DOI:10.1080/17568919.2025.2561395

Saqib Khan, Muhammad Yaqoob, Muhammad H H B Asad, Rafia Falak, Zaman Ashraf, Abdul Mannan, Syed M Bukhari, Fiaz Alam, Umer Rashid

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引用次数: 0

Abstract

Aim: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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强效4-氨基苯磺酰胺衍生物抗蛇毒碱性磷酸酶（ALP）电位。

目的：蛇毒诱导的碱性磷酸酶（ALP）酶在中毒后对受害者的有害影响已被证实。因此，本研究旨在评估4-氨基苯磺酰胺衍生物对眼镜蛇毒液诱导的ALP酶的有效性。方法：合成目标衍生物，通过FTIR、1H NMR、13C NMR进行表征，对接目标蛋白技术。此外，合成类似物在体外评估其抑制ALP活性的潜力。结果：在所合成的化合物中，（SB-5）对目标酶表现出显著的抑制活性（94%,IC50, 3.25µM, p）。结论：本研究证实了4-氨基苯磺酰胺衍生物（SB-5）作为一种有前景的ALP抑制剂的有效性，并作为未来药物开发的主要候选物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Future medicinal chemistry CHEMISTRY, MEDICINAL-

CiteScore

5.80

自引率

2.40%

发文量

118

审稿时长

4-8 weeks

期刊介绍： Future Medicinal Chemistry offers a forum for the rapid publication of original research and critical reviews of the latest milestones in the field. Strong emphasis is placed on ensuring that the journal stimulates awareness of issues that are anticipated to play an increasingly central role in influencing the future direction of pharmaceutical chemistry. Where relevant, contributions are also actively encouraged on areas as diverse as biotechnology, enzymology, green chemistry, genomics, immunology, materials science, neglected diseases and orphan drugs, pharmacogenomics, proteomics and toxicology.