Exploring the anticancer potential of thiadiazole derivatives of substituted thiosemicarbazones formed via copper‐mediated cyclization

Abstract

A couple of N‐(4)‐morpholine/pyrrolidine‐substituted thiosemicarbazones (TSCs) of fluorene‐2‐carboxaldehyde (FM and FP), and their corresponding thiadiazoles (TDZs) (CFM and CFP), were synthesized and characterized (elemental analysis, ultraviolet–visible [UV–Visible], Fourier transform infrared [FT‐IR], nuclear magnetic resonance [NMR; 1H & 13C], high‐resolution mass spectrometry [HRMS], and single‐crystal X‐ray diffraction [SCXRD]) for the evaluation of their anticancer potential. The TDZs were obtained unexpectedly and are possibly formed via single‐step metal (copper)‐mediated oxidative cyclizations of the TSCs. The synthesized compounds are fairly stable in phosphate buffer at the biological pH of 7.4. The density functional theory [DFT] studies were performed to predict the optimized structures and physicochemical properties of these compounds. The compounds were further subjected to computational and experimental biomolecular investigations in order to evaluate their anticancer activity in detail. CFM had the most potent activity against human breast adenocarcinoma (MCF‐7) and human urinary bladder (T24) cancer cells, with IC50 values of 12.00 and 24.80 μM, respectively. In contrast, CFM had negligible cytotoxicity (IC50 = 98.70 μM) against kidney epithelial cells extracted from an African green monkey (Vero) normal cells. This outcome was preferable to that of the widely used medicine Cisplatin. Molecular docking studies were performed with the breast cancer protein “cytochrome P450 1A1” (CYP1A1) and bovine serum albumin (BSA) to predict how effectively the compounds bind to the receptor. The ADMET findings suggest that these compounds have considerable drug‐likeness and oral bioavailability. These insights may open the door for additional medical research into the bioactivities of TSCs and TDZs produced from bioactive carbonyl compounds.

Unraveling the Anticancer Efficacy and Biomolecular Properties of Ru(II)-Arene Complexes of Pyrene-Based Thiosemicarbazone Ligands: A Comprehensive In Silico/In Vitro Exploration

“…Ru-arene complexes, cisplatin, NAMI-A, and KP1019 were tested for cytotoxicity using MTT assay against MCF-10a normal breast cells and human breast cancer (MDA-MB-231), lung cancer (A459), and cervical cancer (HeLa) cell lines. 30 The experimental protocol is described in depth in the appendices (Section S10).…”

Biomolecular Interactions and Anticancer Mechanisms of Ru(II)-Arene Complexes of Cinnamaldehyde-Derived Thiosemicarbazone Ligands: Analysis Combining In Silico and In Vitro Approaches

“…The molecular electrostatic potential (MEP) surface of RuPCAM , in addition to all other complexes, is depicted in Figure . The electron density is primarily concentrated around the sulfur atom and the five-membered ring formed during coordination (with the color red denotes areas rich in electrons, the color blue denotes areas low in electrons, and green denotes the neutral area) . This means that the complexes’ sulfur and five-membered ring are likely to interact strongly with biomolecules like proteins.…”

“…Furthermore, this induced planarity of S13−C12−N11−N10 in RuPCAM could also enhance the ligand to metal charge transfer (LMCT), 44 which is very evident in the absorption spectra of RuPCAM (see supplementary the sulfur atom and the five-membered ring formed during coordination (with the color red denotes areas rich in electrons, the color blue denotes areas low in electrons, and green denotes the neutral area). 45 This means that the complexes' sulfur and five-membered ring are likely to interact strongly with biomolecules like proteins.…”

New 1,3,4-Thiadiazole Derivatives as α-Glucosidase Inhibitors: Design, Synthesis, DFT, ADME, and In Vitro Enzymatic Studies

“…Due to the presence of the N–C–S moiety, 1,3,4-thiadiazole derivatives are thought to have different biological activities . Authors recommend that the 1,3,4-thiadiazole derivative’s biological activities are shown due to the strong aromaticity of the ring, in vivo stability, and thiadiazole had less to zero toxicity for higher vertebrates, which includes humans for the treatment of cancer. , The aromatic five-membered ring of thiadiazole contains two nitrogen atoms and one sulfur atom. It also has a two-electron donor system and a hydrogen bonding domain, allowing it to act as an anhydrase …”