New efficient design and synthesis of novel antioxidant and antifungal 7-imino[1,3]selenazolo[4,5- d ]pyrimidine-5(4 H )
- PDF / 841,675 Bytes
- 7 Pages / 595.276 x 790.866 pts Page_size
- 113 Downloads / 235 Views
ORIGINAL PAPER
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 Seddigheh Sheikhi‑Mohammareh1 · Ali Shiri1 · Hamid Beyzaei2 · Elahe Yarmohammadi2 Received: 17 March 2020 / Accepted: 5 May 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020
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 C 2-pyrrolidine and C 2-piperidine both with I C50 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. Graphic abstract
Keywords Selenazoles · Phenyl isothiocyanates · One-pot synthesis · Selenium-containing heterocycles · Antioxidant · Antifungal Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00706-020-02617-2) contains supplementary material, which is available to authorized users. * Ali Shiri [email protected] 1
Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
Department of Chemistry, Faculty of Science, University of Zabol, Zabol, Iran
2
Introduction Selenium oligoelement (Se) is included in very important components of the human body such as selenoproteins [1]. The most notable example is glutathione peroxidase which is important antioxidant in neuronal defense against oxidative stress [2]. Selenium atom has been also found in the
13
Vol.:(0123456789)
S. Sheikhi‑Mohammareh et al.
structure of one of the most well-known anti-cancer and antiviral drugs selenazof
Data Loading...
