Synthesis, cytotoxicity and antifungal activity of 5-nitro-thiophene-thiosemicarbazones derivatives

Abstract

In the present work, twelve N-substituted 2-(5-nitro-thiophene)-thiosemicarbazones derivatives (L1-12) were synthesized, characterized and their in vitro cytotoxic and antifungal activities were evaluated against Candida sp. and Cryptococcus neoformans. The probable mechanisms of action have been investigated by sorbitol and ergosterol assays. Additionally, ultrastructural study by Scanning Electron Microscopy was performed with the L10 compound. All compounds were obtained in good yield and their chemical structures were characterized on basis of their physico-chemical and Nuclear Magnetic Resonance - NMR, Spectrophotometric Absorption in the Infrared - IR and High-resolution Mass Spectrometry - HRMS data. The results showed that all strains were more sensitive to the compound L10 except Candida tropicalis URM 6551. On the other hand, the cytotoxicity assay by incorporation of tritiated thymidine showed moderate cytotoxic activity on L8 of the 50 μg/mLat which had the best MIC-cytotoxicity relationship. Concerning the study of the possible mechanism of action, the compounds were not able to bind to ergosterol in the membrane, do not act by inhibiting the synthesis of fungal cell wall (sorbitol assay). However, the Scanning Electron Microscopy - SEM analysis shows significant morphological changes in shape, size, number of cells and hyphae, and cell wall indicating a possible mechanism of action by inhibition of enzymes related to the ergosterol biosynthesis pathway. Our results demonstrate that N-substituted 2-(5-nitro-thiophene)-thiosemicarbazones derivatives are potential antifungal agents with activity associated with inhibition of enzymes related to biosynthesis of ergosterol.

SR9009 has REV-ERB–independent effects on cell proliferation and metabolism

“…The mechanisms by which SR9009 and related compounds exert pleiotropic effects on cell proliferation, metabolism, and gene expression in the absence of REV-ERBs remain to be determined. Of note, both SR9009 and SR9011 contain known toxicophores, such as nitrothiophene moieties, as active groups (46,47). In any case, the fact that many of the effects of SR9009 are REV-ERB-independent has several important implications.…”

Biological Applications of Co(II) and Ni(II) Complexes of Semicarbazones and Thiosemicarbazones

“…The biological importance of these Schiff's base chelates of thiosemicabazides involved the researchers greater than before to develop fresh ligands as antibacterial [16], antimicrobial [17][18][19], antifungal [20,21], antiparasitic [22], antitumor [23], anticancer [24][25][26], antioxidant [27,28], anti-inflammatory [29], anti-HIV [30], antiproliferative [31], antileishmanial activities [32] and antiviral [33]. Tetradentate thiosemicabazone with strong DNA-binding ability was isolated after the condensation of pyruvaldehyde with 4-(aryl)-thiosemicarbazones [34].…”

Synthesis, characterization, antifungal and antibacterial activities evaluation of copper (II), zinc (II) and cadmium (II) chloride and bromide complexes with new (E)‐1‐(3,4‐dimethoxybenzylidene)‐4‐methylthiosemicarbazone ligand

“…Thiosemicarbazone (TSC) derivatives can adopt various coordination modes as N , S ‐donors, and their transition metal complexes have been studied because of their biological [ 1–3 ] and pharmaceutical [ 4,5 ] activities. TSCs and their metal complexes have been demonstrated to exhibit high biological activity against malarial, [ 6–8 ] bacterial [ 9 ] and fungal infections, [ 9,10 ] and displayed promising antitumor activity against various cancer cell lines.…”