Abstract
Mannich bases and its derivatives are regarded as supreme pharmacophores in therapeutics. The study investigates the antimycotic potential of Mannich bases, 1-((1H-benzimidazol-1-yl) methyl) urea (C1) and 1-((3-hydroxynapthalen-2-yl) methyl) thiourea (C2), against Candida albicans. Biofilm and hyphal inhibitory activities of the Mannich bases were tested by crystal violet quantification, fluorescence imaging cAMP rescue, qRT PCR, and by molecular docking analysis. The compounds inhibited the biofilms of C. albicans and restrained the filamentation abilities of the pathogen. Structure-activity relationship studies revealed that the presence of urea or thiourea moiety in the tail section is essential for interacting with adenylate cyclase (AC). The Mannich bases seemed to block Ras-cAMP-PKA pathway by inhibiting second messenger activity required for hyphal induction and biofilm formation. In conclusion, the study warrants point-of-care testing of C1/C2 and provides a starting point for deriving several structurally modified Mannich bases which might plausibly replace the prevailing antimycotic drugs in future.
Highlights
Candida albicans is the most prevalent pathogenic yeast known to cause a diverse spectrum of systemic and chronic infections in human[1]
They often act as chemical leads for the synthesis of new pharmacophores or drugs with medicinal values
This study identifies few newly synthesized Mannich bases as an antimycotic drug against the opportunistic pathogen, C. albicans
Summary
Satish Kumar Rajasekharan[1], Chakkaravarthi Kamalanathan[1], Vinothkannan Ravichandran[2], Arvind Kumar Ray[3], Ann Susan Satish4 & Sucharitha Kannappan Mohanvel[5]. The Mannich bases seemed to block Ras-cAMP-PKA pathway by inhibiting second messenger activity required for hyphal induction and biofilm formation. Biofilm formation and hyphal transition are the major virulence traits in C. albicans which remain as the vital etiological factors of candidiasis[3] This ability allows the pathogen to adhere to host cells, invade into intestinal epithelium and colonize to form sessile phenotypes[4]. Cyr[1], is an enzyme which is shown to regulate several developmental and virulence factors in C. albicans[12,13] These include hyphal filamentations, white-opaque phenotypic switching, and biofilm formations[13]. Mannich bases are end products of a nucleophilic addition reaction termed as a Mannich reaction, and are often referred to as beta-amino ketones These synthetic chemicals have played a vital role in the development of medicinal and pharmaceutical chemistry as well. In-depth analysis was performed to identify and elucidate the mode of action of the lead compound by molecular docking, quantitative PCR, and cAMP rescue assays
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
