Synthesis and Characterization of a New Class of Chromene-Azo Sulfonamide Hybrids as Promising Anticancer Candidates with the Exploration of Their EGFR, hCAII, and MMP-2 Inhibitors Based on Molecular Docking Assays.

In this study, novel selective antitumor compounds were synthesized based on their fundamental pharmacophoric prerequisites associated with EGFR inhibitors. A molecular hybridization approach was employed to design and prepare a range of 4H-chromene-3-carboxylates 7a-g, 8, and 11a-e derivatives, each incorporating a sulfonamide moiety. The structures of these hybrid molecules were verified using comprehensive analytical and spectroscopic techniques. During the assessment of the newly synthesized compounds for their anticancer properties against three tumor cell lines (HepG-2, MCF-7, and HCT-116), compounds 7f and 7g displayed remarkable antitumor activity against all tested cell lines, outperforming the reference drug Cisplatin in terms of efficacy. Consequently, these promising candidates were selected for further investigation of their anti-EGFR, hCAII, and MMP-2 potential, which exhibited remarkable effectiveness against EGFR and MMP2 when compared to Sorafenib. Additionally, docking investigations regarding the EGFR binding site were implemented for the targeted derivatives in order to attain better comprehension with respect to the pattern in which binding mechanics occur between the investigated molecules and the active site, which illustrated a higher binding efficacy in comparison with Sorafenib.

DFT and In-silico Investigations, along with In-vitro Antitumor and Antimicrobial Assessments of Pharmacological Molecules.

BACKGROUND: Molecules bearing an active methylene bridge are one of the most fruitful and remarkable precursors that have been incorporated into the synthetic strategy of an assortment of bioactive compounds. OBJECTIVE: The reactive methylene derivatives have been endowed with multiple reactions, which target biological and medicinal applications and result from their structural diversity and discrete reactivity. METHODS: The present report endeavors to synthesize, characterize, and in-vitro evaluate several novel propanoic acids, coumarin, and pyrazole derivatives as antimicrobial and antiproliferative agents. The in-silico molecular docking, physicochemical, pharmacokinetic/ADMET, bioactivity, and drug-likeness predictions were conducted for all the synthesized compounds. RESULTS: The highest docking score is -9.9 and -8.3 kcal/mol, respectively, for compound 9 (azocoumarin) and 13 (acrylic acid derivative) with the target proteins E. coli topoisomerase II, DNA gyrase subunit B and PI3K p110α domain, respectively. Moreover, this study predicts the synthesized molecules that may inhibit the novel COVID-19, obtained through virtual screenings only, where compounds 9, 13, 14, 17, and 19 came to the limelight with good docking scores i.e., more than -8 Kcal/mol. Safety profiling of the most potent compound 9 was utilized against normal cell lines and the hemolytic effect on RBCs. CONCLUSION: The in-silico ADMET studies of the synthesized compounds revealed moderate to good -likeness, high gastro intestinal (GI) absorption, and inhibiting the Cytochrome CYP2C19 and CYP2C9 and all the derivatives possess non-cancerous nature. The in-vitro screening demonstrated that several of the novel molecules are promising drug candidates. The density functional theory (DFT) theoretical calculations were performed to calculate the energy levels of the FMOs and their energy gaps, dipolemoment, andmolecular electrostatic potential. Such parameters, along with the physicochemical parameters, could be a good tool to confirm biological activity.

Development of Polyvinyl Alcohol/Kaolin Sponges Stimulated by Marjoram as Hemostatic, Antibacterial, and Antioxidant Dressings for Wound Healing Promotion.

The predominant impediments to cutaneous wound regeneration are hemorrhage and bacterial infections that lead to extensive inflammation with lethal impact. We thus developed a series of composite sponges based on polyvinyl alcohol (PVA) inspired by marjoram essential oil and kaolin (PVA/marjoram/kaolin), adopting a freeze-thaw method to treat irregular wounds by thwarting lethal bleeding and microbial infections. Microstructure analyses manifested three-dimensional interconnected porous structures for PVA/marjoram/kaolin. Additionally, upon increasing marjoram and kaolin concentrations, the pore diameters of the sponges significantly increased, recording a maximum of 34 ± 5.8 µm for PVA-M0.5-K0.1. Moreover, the porosity and degradation properties of PVA/marjoram/kaolin sponges were markedly enhanced compared with the PVA sponge with high swelling capacity. Furthermore, the PVA/marjoram/kaolin sponges exerted exceptional antibacterial performance against Escherichia coli and Bacillus cereus, along with remarkable antioxidant properties. Moreover, PVA/marjoram/kaolin sponges demonstrated significant thrombogenicity, developing high thrombus mass and hemocompatibility, in addition to their remarkable safety toward fibroblast cells. Notably, this is the first study to our knowledge investigating the effectiveness of marjoram in a polymeric carrier for prospective functioning as a wound dressing. Collectively, the findings suggest the prospective usage of the PVA-M0.5-K0.1 sponge in wound healing for hemorrhage and bacterial infection control.