Synthesis of proline derived benzenesulfonamides: A potent anti-Trypanosoma brucei gambiense agent

European Journal of Medicinal Chemistry
David Izuchukwu UgwuNarendra Kumar Mishra

Abstract

Thousands of death in Africa and other developing nations are still attributed to trypanosomiasis. Excessive sleep has been associated with increased inflammation. We report herein, the synthesis, antitrypanosomal and anti-inflammatory activities of eight new carboxamide derivatives bearing substituted benzenesulfonamides. The base promoted reactions of l-proline and L-4-hydroxyproline with substituted benzenesulfonyl chlorides gave the benzenesulfonamides (11a-h) in excellent yields. Boric acid mediated amidation of the benzenesulfonamides (11a-h) and p-aminobenzoic acid (12) gave the new carboxamides (13a-h) in excellent yields. The new carboxamides were tested for their antitrypanosomal and anti-inflammatory activities against Trypanosome brucei gambiense and inhibition of carrageenan-induced rat paw edema. Compound 13f was the most potent antitrypanosomal agent with an IC50 value of 2 nM as against 5 nM for melarsoprol; whereas compound 13a was the most potent anti-inflammatory agent with percentage inhibition of carrageenan-induced rat paw edema of 58, 60, 67 and 84% after 0.5 h, 1 h, 2 h and 3 h administration respectively. The structure-activity relationship study revealed that substitution at the para position in the be...Continue Reading

Citations

Mar 10, 2020·Acta Crystallographica. Section E, Crystallographic Communications·Brock A StenforsFelix N Ngassa
Aug 31, 2021·Frontiers in Cell and Developmental Biology·Eduardo J PatriarcaGabriella Minchiotti
Jan 19, 2022·Drug Development Research·Cauê Benito Scarim, Fernando Rogério Pavan

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