Recent studies have highlighted the 1,3,4-oxadiazole scaffold as an important pharmacophore present in numerous biologically active molecules and therapeutic agents. In continuation of our interest in biologically active heterocyclic compounds, we report the synthesis of a series of novel 2,5-di(aryl/heteroaryl)-1,3,4-oxadiazoles using molecular iodine (1.0 equiv.) under basic conditions. The synthesized compounds were evaluated for in vitro anticancer and antifungal activities together with comprehensive computational investigations. Cytotoxicity studies against normal HEK-293 cells and the cancer cell lines DU145, HepG2, and B16–F10 demonstrated diverse activity profiles, with compounds 9b and 9g exhibiting the most favourable cytotoxic activity and selectivity, while compound 9r showed moderate activity. Antifungal evaluation of the nineteen synthesized derivatives against Alternaria solani (MTCC-2101), Pyricularia oryzae (MTCC-1477), Helminthosporium solani (MTCC-1899), and Fusarium oxysporum (MTCC-2087) revealed a limited, strain-dependent antifungal activity against selected fungal strains. ADME and drug-likeness analyses, using Erlotinib as a reference, indicated acceptable physicochemical and pharmacokinetic characteristics for the synthesized compounds. Comparative molecular docking studies against human DNA topoisomerase IIα (TOP2A), histone deacetylase 2 (HDAC2), and thymidine phosphorylase demonstrated favourable binding interactions, particularly for compounds 9b and 9g. Subsequent 200 ns molecular dynamics simulations, MM-GBSA binding free-energy calculations, and free energy landscape analyses consistently supported the stability of the corresponding protein–ligand complexes and identified TOP2A and HDAC2 as the most plausible molecular targets underlying the observed cytotoxic activity. Collectively, the integrated experimental and computational findings identify 9b and 9g as promising lead 1,3,4-oxadiazole derivatives for further development as anticancer agents.
Thongolla Ramesha, T. Shenoy, Ummareddy Venkata et al.· RSC Advances· 0 citations
Hydrazones have gained significant attention in the field of medicinal chemistry because of their ease of preparation, crystalline nature, structural flexibility and broad-spectrum biological activity. Additionally, N-containing heterocycles have always contributed to anticancer drug discovery, with 73% of FDA-approved anticancer drugs based on them. Recently, the idea of hybrid drug design that synergistically combines two or more pharmacologically active molecules has become an effective strategy in discovering new anticancer drugs. Hence, combining two bioactive fragment hydrazones and N-containing heterocycles can be considered an effective strategy for discovering potent anticancer drugs. Among these, heterocycle–hydrazone hybrids derived from quinoline, indole, triazole, benzimidazole and isatin have displayed promising anticancer activities, with some of the studies even approaching in vivo evaluation. Overall, this review focuses on the anticancer activities of these hydrazone hybrids, their in vitro cytotoxic results, the proposed mechanism of action of the most active compound, cell death pathway results, docking studies, and cell cycle-arrest results. In addition, various synthetic strategies of hydrazones, including conventional methods, microwave and ultrasonication irradiation techniques, diazonium salt-derived methods and solvent-free reaction conditions, have been reported. Furthermore, the kinetics of hydrazone synthesis is described in brief.
K. Pai, K. Bhat, Nagaraj Pai et al.· RSC Advances· 0 citations
The development of bio-based antibacterial materials using natural additives is a crucial strategy for reducing reliance on hazardous synthetic chemicals. This study investigated the effect of incorporating ginger nanoparticles (GNPs) at varying concentrations (1, 2, 3, and 4 mL) into a chitosan/polyethylene oxide (PEO) blend to enhance its antibacterial properties. XRD analysis revealed that hydrogen bonding between chitosan and PEO produced a broad peak at 23.60°. The addition of the GNPs intensified this peak and introduced a sharper feature at 19.00°, confirming the successful interaction between the nanoparticles and the polymer matrix. FTIR spectroscopy showed new C–O–C vibrational bands at 1107 cm−1 upon blending, with further spectral changes observed after GNP addition, indicating the formation or disappearance of specific functional groups. The incorporation of the GNPs was demonstrated by a new absorption peak at 235 nm, and the semi-crystalline nature of the nanocomposite was confirmed by optical analysis. TEM revealed that the GNPs had diameters of 36.6 ± 13.8 nm, while zeta potential analysis at 25 °C recorded count rates of 106.8, 71.90, and 83.50 kcps for three distinct particle bands, and the mean was −19.33 mV, with a zeta potential deviation of 14.0 mV. The value of the zeta potential indicated the moderate stability of the GNPs. SEM demonstrated that increasing the GNP concentration led to larger, aggregated particle morphologies, with complete coalescence at the highest concentration. The chitosan/PEO blend exhibited higher thermal stability than pure chitosan, while the final polymer nanocomposite showed reduced residue levels at elevated temperatures. Antibacterial testing against Gram-positive (Enterococcus and Staphylococcus aureus) and Gram-negative (Escherichia coli and Klebsiella) bacteria demonstrated that the GNP-loaded nanocomposite exhibited enhanced antimicrobial activity compared with the pure polymer blend. For Gram-negative bacteria, the activity was small or negligible. These results position the chitosan/PEO/GNP nanocomposite as a promising bio-based material for antibacterial applications.
Ghada A Mostafa, D. M. Ayad, A. A. Menazea et al.· RSC Advances· 0 citations
Overall, the cytotoxic effects of 7k on MV4-11 cells are attributed to the coordinated induction of ROS-mediated oxidative stress, G0/G1 cell cycle arrest, and caspase-dependent apoptosis, highlighting its promising antiproliferative potential.