☆ 4.5 Article

Carbonic anhydrase inhibitors. The X-ray crystal structure of human isoform II in adduct with an adamantyl analogue of acetazolamide resides in a less utilized binding pocket than most hydrophobic inhibitors

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2010)

期刊

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷 20, 期 15, 页码 4376-4381

出版社

PERGAMON-ELSEVIER SCIENCE LTD

DOI: 10.1016/j.bmcl.2010.06.082

关键词

Carbonic anhydrase; Sulfonamide; 1,3,4-Thiadiazole-2-sulfonamide; X-ray crystallography; Enzyme-inhibitor; Isoforms I-XV

类别

Chemistry, Medicinal Chemistry, Organic

资金

European Union
NIH [GM2515, GM25154]
Thomas Maren grant

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摘要

We investigated the inhibitory activity of several 1,3,4-thiadiazole-sulfonamides against all catalytically active CA (EC 4.2.1.1), CA I-XV. The tail derivatizing the 5-position in the 1,3,4-thiadiazole-2-sulfonamide scaffold was observed to be critical as an inhibitory determinant of these compounds. The high resolution X-ray crystal structure of hCA II in complex with 5-(1-adamantylcarboxamido)-1,3,4-thiadiazole-2-sulfonamide, showed the adamantyl moiety of the inhibitor residing in a less utilized binding pocket than that of most hydrophobic inhibitors, lined by the amino acid residues Ile91, Val121 and Phe131. This binding site may explain the diverse inhibition profiles of 5-carboxamide- and sufonamide-derivatized 1,3,4-thiadiazole-2-sulfonamides and offers a hot spot for designing isoform selective inhibitors, considering that residues 91 and 131 are highly variable among the 13 catalytically active isoforms. (C) 2010 Elsevier Ltd. All rights reserved.

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The potential of Rhein's aromatic amines for Parkinson's disease prevention and treatment: α-Synuclein aggregation inhibition and disaggregation of preformed fibers

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Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2024)

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Article Chemistry, Medicinal

Design, synthesis and biological evaluation of novel cationic liposomes loaded with melphalan for the treatment of cancer

Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla

Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2024)

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