Synthesis, Cytotoxicity, and Photophysical Investigations of 2-Amino-4,6-diphenylnicotinonitriles: An Experimental and Theoretical Study.

In this study, we present a comprehensive investigation of 2-amino-4,6-diphenylnicotinonitriles (APNs, 1-6), including their synthesis, cytotoxicity against breast cancer cell lines, and photophysical properties. Compound 3 demonstrates exceptional cytotoxicity, surpassing the potency of Doxorubicin. The fluorescence spectra of the synthesized 1-6 in different solvents reveal solvent-dependent shifts in the emission maximum values, highlighting the influence of the solvent environment on their fluorescence properties. A quantum chemical TD-DFT analysis provides insights into the electronic structure and fluorescence behavior of 1-6, elucidating HOMO-LUMO energy gaps, electronegativity values, and dipole moments, contributing to a deeper understanding of their electronic properties and potential reactivity. These findings provide valuable knowledge for the development of APNs (1-6) as fluorescent sensors and potential anticancer agents.

A Facile Synthesis and Molecular Characterization of Certain New Anti-Proliferative Indole-Based Chemical Entities.

Cancer cells frequently develop drug resistance, which leads to chemotherapeutic treatment failure. Additionally, chemotherapies are hindered by their high toxicity. Therefore, the development of new chemotherapeutic drugs with improved clinical outcomes and low toxicity is a major priority. Several indole derivatives exhibit distinctive anti-cancer mechanisms which have been associated with various molecular targets. In this study, target compounds 4a-q were obtained through the reaction of substituted benzyl chloride with hydrazine hydrate, which produces benzyl hydrazine. Subsequently, the appropriate substituted benzyl hydrazine was allowed to react with 1H-indole-2-carboxylic acid or 5-methoxy-1H-indole-2-carboxylic acid using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide as a coupling agent. All compounds exhibited cytotoxicity in three cell lines, namely, MCF-7, A549, and HCT. Compound 4e exhibited the highest cytotoxicity, with an average IC50 of 2 µM. Moreover, a flow cytometry study revealed a significantly increased prevalence of Annexin-V and 7-AAD positive cell populations. Several derivatives of 4a-q showed moderate to high cytotoxicity against the tested cell lines, with compound 4e having the highest cytotoxicity, indicating that it may possess potential apoptosis-inducing capabilities.

Design, Synthesis, and Antimicrobial Activity of Certain New Indole-1,2,4 Triazole Conjugates.

The increasing prevalence of microbial infections and the emergence of resistance to the currently available antimicrobial drugs urged the development of potent new chemical entities with eminent pharmacokinetic and/or pharmacodynamic profiles. Thus, a series of new indole-triazole conjugates 6a-u was designed and synthesized to be assessed as new antimicrobial candidates using the diameter of the inhibition zone and minimum inhibitory concentration assays against certain microbial strains. Their in vitro antibacterial evaluation revealed good to moderate activity against most of the tested Gram-negative strains with diameter of the inhibition zone (DIZ) values in the range of 11-15 mm and minimum inhibition concentration (MIC) values around 250 µg/mL. Meanwhile, their in vitro antifungal evaluation demonstrated a potent activity against Candida tropicalis with MIC value as low as 2 µg/mL for most of the tested compounds. Moreover, compound 6f is the most potent congener with an MIC value of 2 µg/mL against Candida albicans.

Synthesis, molecular docking and preliminary in-vitro cytotoxic evaluation of some substituted tetrahydro-naphthalene (2',3',4',6'-tetra-O-acetyl-ß-D-gluco/-galactopyranosyl) derivatives.

A facile, convenient and high yielding synthesis of novel S-glycosides and N-glycosides incorporating 1,2,3,4-tetrahydronaphthalene and or 1,2-dihydropyridines moieties has been described. The aglycons 2, 4, and 7 were coupled with different activated halosugars in the presence of basic and acidic medium. The preliminary in-vitro cytotoxic evaluation revealed that compounds 3c, 3f, 5c and 7b show promising activity. A molecular docking study was performed against tyrosine kinase (TK) (PDB code: 1t46) by Autodock Vina. The docking output was analyzed and some compounds have shown hydrogen bond (H-B) formation with reasonable distances ranged from 2.06 A° to 3.06 A° with Thr 670 and Cys 673 residues found in the specified pocket. No hydrogen bond was observed with either Glu 640 nor Asp 810 residues, as was expected from pdbsum.