New efficient design and synthesis of novel antioxidant and antifungal 7-imino[1,3]selenazolo[4,5-d]pyrimidine-5(4H)-thiones utilizing a base-promoted cascade addition/cyclization sequence

Abstract

A straightforward strategy for the efficient synthesis of multi-functionalized 7-imino[1,3]selenazolo[4,5-d]pyrimidine-5(4H)-thiones bearing an incorporated N-phenylmethanethioamide fragment from the heteroannulation of several 2,4,5-trisubstituted 1,3-selenazoles with readily accessible phenyl isothiocyanates was established in boiling pyridine. To enrich the biological profile of the newly synthesized fused heterocyclic scaffold, some noted pharmacophores such as pyrrolidine, piperidine, morpholine, fluorine, and bromine were inserted into the framework. Inhibitory activities of the selenium-containing heterocycles were assessed against DPPH and Candida albicans. Antioxidant activities as IC50 values were observed in the range of 0.010–0.063 mM. Results revealed that 6-phenyl-substituted selenazolopyrimidines bearing C2-pyrrolidine and C2-piperidine both with IC50 value of 0.010 mM were superlative amongst others. Being far superior to ascorbic acid (IC50 = 0.022 mM), 4-fluorophenyl-substituted compounds bearing 2-morpholine residual (IC50 = 0.014 mM), and 2-piperidine (IC50 = 0.019 mM) were ranked in the second place and third place of antioxidant efficacy, respectively. Moreover, para-bromo and fluoro substituted N-phenylselenazolo[4,5-d]pyrimidines containing pyrrolidine moiety exhibited similar and six times higher potency for death and blocking of Candida albicans fungus than ketoconazole, respectively. Consequently, some of these selenazolopyrimidines are promising anti-Candida albicans as well as antioxidant lead compounds which can be used in the treatment of candidiasis, cancer, and neurodegenerative and diabetes diseases.