Design and structure-activity relationships anticandidosic of diazaheteroaryl functionalized by Michaël acceptors

Document Type : Original Article

Authors

1 Department of Therapeutic Chemistry and Organic Chemistry, UFR SPB, FHB University, Abidjan, Ivory Coast.

2 Department of Chemistry, UFR Environment, Jean Lorougnon Guédé University, Daloa, Ivory Coast.

3 UFR of Biological Sciences, Péléforo Gon Coulibaly University, Korhogo, BP 1328 Korhogo, Ivory Coast.

4 Swiss Center for Scientific Research in Côte d'Ivoire, 01 BP 1303 Abidjan, Ivory Coast.

5 Laboratory of Organic Chemistry and Natural Substances, UFR SSMT, FHB University, Abidjan, Ivory Coast.

Abstract

The management of candidiasis, once effective, is becoming more and more difficult with the increase of resistance of various Candida species to classical antifungals. It is in this context that we reported in our previous works the pharmacochemical development of new diazaheteroaryls derivatives functionalized with a Michaël acceptor such as arylpropenone, arylacrylonitrile and arylcyanopropenone. These diazaheteroaryls derivatives with benzimidazolyl-arylpropenone or benzimidazolyl-arylacrylonitriles or benzimidazolyl-arylcyanopropenone and imidazopyridinyl-arylpropenones structure were obtained by chemical synthesis and then characterized by the usual spectroscopic methods (NMR and MS). The anticandidosic activities of these derivatives expressed as Minimum Inhibitory Quantity (MIQ) were determined in vitro on a clinical strain of Candida albicans, following the bioautography technique. The results show that diazaheteroaryls functionalized by a Michael acceptor have remarkable activities with IMQ ranging from 10 to 0.16 µg. Moreover, the anticandidosic performance of the different derivatives were related to the nature of the Michael acceptor and the structural variations undertaken on the benzene homocycle. This paper, which is the synthesis of a decade of research by our team, will address the pharmacochemical design, chemical synthesis and overall serial structure-anticandidosic activity studies of diaza-heteroaryls functionalized with a Michael acceptor in order to propose compounds that can be developed as anticandidosic drug candidates.

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  • Receive Date: 21 July 2021
  • Revise Date: 29 December 2021
  • Accept Date: 20 September 2021
  • First Publish Date: 20 September 2021