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Cyclic diselenide-based coumarin compound 4-methyl-7-((naphtho [1,8-cd][1,2]diselenol-3-ylmethylene)amino)-2H-chromen-2-one (probe) was successfully synthesized and characterized using 1H, 13C NMR, HRMS, and FT-IR spectroscopy. The probe endured systematic evaluation against a broad panel of reactive oxygen species (ROS) and biothiols, revealing exceptional selectivity and sensitivity for superoxide relative to other tested analytes. The probe has a lower detection limit of 32 nM for superoxide, as determined through the fluorescence titration method, with a high stock shift of 74 nm. Comparative study revealed that the probe possessed a quantum yield of 1.22%, which increased to 27.3% following reaction with superoxide, indicating a 22-fold increment in fluorescence intensity once oxidised by superoxide. The Density Functional Theory (DFT) studies have predicted that the probe is present in cis conformation with the SeN (imine) bonding. The mechanism of the conversion of the cis-trans isomers of the probe has been investigated, and the interconversion between predicted possible oxidation products is confirmed via combined spectroscopic monitoring (UV-Vis and fluorescence time-course studies), supported by theoretical analysis experimentally. In vitro cell viability assays confirmed that the probe is biocompatible with normal MDCK cells while revealing potent anti-cancer effects against cancerous cells (HeLa and MCF7).
Quinoline-based “turn-on” fluorescent probe was successfully synthesized using 5-amino quinoline and 2-(phenylselanyl)benzaldehyde. The probe was found to be selective for superoxide over other reactive oxygen species (ROS) and biothiols. The probe can detect superoxide in the presence of other ROS and biothiols. The detection limit of the probe for superoxide was found to be 37 nM with a Stokes shift of 150 nm. The probe quickly detects superoxide with a 21-fold increase in fluorescence intensity. The probe exhibited anticancer activity on HeLa cells that was comparable to the standard drug (Cisplatin). Organoselenium based quinoline probe was developed. The probe was selective for superoxide with instant response and possess good anticancer activity.
A simple and promising methodology was employed for the synthesis of (Z)-1-(benzo[d]thiazol-2-yl)-2-(3-substituted thiazolidine-4-one) hydrazine as antitubercular agents. In vitro activity was tested against Mycobacterium tuberculosis. Two derivatives among all the synthesized compounds were found to be highly effective. Furthermore, to rationalize the observed biological activity data, a molecular docking study has also been carried out against a potential target DprE1 enzyme. The interaction was shown between the oxygen of thiazolidinediones and Ser228. The bond distance (O—H) is 2.35 Å. The π-π-stacking was seen between His137 and thiazole ring electrons. The binding score of compound 15 is –7 kcal/mol, which suggests an excellent binding affinity toward the Dpre1 receptor.
In search of new biologically potent molecules a small focused library of new guanidine-1,2,3-triazole hybrid derivatives were synthesized via Organocatalytic enolate- mediated azide-carbonyl [3 + 2] cycloaddition yielding a highly functionalized triazole core structure. The synthesis of all the derivatives were confirmed by spectral analysis H-1 NMR, C-13 NMR and MS. The new guanidine-1,2,3-triazole conjugates were found to exhibit promising anti-inflammatory and antioxidant activity. The anti-inflammatory activity screened by membrane stabilization method summarizes the four potential conjugates 5c, 5f, 5h and 5g to be potent in comparison with standard drug Diclofenac sodium (DFS). The conjugates were also assessed for antioxidant potential by DPPH method. Among all the synthesized compounds, the compounds 5d, 5f, 5g and 5h exhibited potent antioxidant activity. Molecular docking study was performed to gain insight into the putative binding mode and binding strength of these compounds with the target enzyme Cyclo-oxygenase (COX-2) enzyme. The in vitro and in silico studies together with simpler designing and synthesis strategy via Organocatalytic enolate- mediated azide-carbonyl [3 + 2] cycloaddition followed by a two-component reaction with guanidine in basic conditions rationalize guanidine-1,2,3-triazole hybrid derivatives as easily assessable novel therapeutic agents.
Major challenges in current cancer chemotherapy include drug resistance, low efficacy and non-selectivity, resulting in undesirable side effects. In this study, we demonstrate a solution to these challenges that involves a dual targeting approach for tumors that overexpress CD44 receptors. The approach employs a nano-formulation (tHAC-MTX nano assembly), fabricated from hyaluronic acid (HA), the natural ligand for CD44, conjugated with methotrexate (MTX) and complexed with the thermoresponsive polymer 6-O-carboxymethylchitosan (6-OCMC) graft poly(N-isopropylacrylamide) [6-OCMC-g-PNIPAAm]. The thermoresponsive component was designed to have a lower critical solution temperature of 39 °C (the temperature of tumor tissues). In-vitro drug release studies reveal faster release of the drug at the higher temperatures of the tumor tissue likely due to the conformation changes in the thermoresponsive component of the nano assembly. Drug release was also enhanced in the presence of hyaluronidase enzyme. Higher cellular uptake and greater cytotoxicity of the nanoparticles were demonstrated in cancer cells that overexpress CD44 receptors suggesting a receptor binding and cellular uptake mechanism. Such nano-assemblies which incorporate multiple targeting mechanisms have the potential to improve efficacy and decrease side effects of cancer chemotherapy.
