Microwave-Assisted Synthesis, Biological Activity Evaluation, Molecular Docking, and ADMET Studies of Some Novel Pyrrolo [2,3-b] Pyrrole Derivatives

Novel pyrrolo [2,3-b] pyrrole derivatives were synthesized and their hypolipidemic activity was assessed in hyperlipidemic rats. The chemical structures of the new derivatives were confirmed through spectral analysis. Compounds 5 and 6 were revealed to be the most effective hypolipidemic agents, with considerable hypocholesterolemic and hypotriglyceridemic effects. They appear to be promising candidates for creating new powerful derivatives with anti-atherosclerotic and hypolipidemic properties. As for antimicrobial activity, some of the tested compounds showed moderate activity against Pseudomonas aeruginosa: compound 2 revealed an MIC value of 50 μg/mL, compared to 25 μg/mL for ciprofloxacin. Compound 3 showed good antimicrobial activity against Staphylococcus aureus, comparable to ciprofloxacin, and roughly half the activity of ampicillin, according to MIC values. Compound 2 has an MIC approximately 25% of that of clotrimazole against Candida albicans. Compound 2 also showed the highest antioxidant activity with 59% inhibition of radical scavenging activity. Additionally, the cytotoxic activity of these new derivatives 1–7 was investigated and most of them showed good anticancer activity against the three tested cell lines

Thieno[2,3‑<i>b</i>]thiophene Derivatives as Potential EGFR^WT and EGFRT^790M Inhibitors with Antioxidant Activities: Microwave-Assisted Synthesis and Quantitative In Vitro and In Silico Studies

Microwave-assisted synthesis and spectral analysis of certain novel derivatives of 3,4-diaminothieno[2,3-b]thiophene-2,5-dicarbonitrile 1–7 were carried out. Compounds 1–7 were examined for cytotoxicity against MCF-7 and A549 cell lines using the quantitative MTT method, and gefitinib and erlotinib were used as reference standards. Compounds 1–7 were shown to be more active than erlotinib against the two cell lines tested. Compound 2 outperformed regular erlotinib by 4.42- and 4.12-fold in MCF-7 and A549 cells, respectively. The most cytotoxic compounds were subsequently studied for their suppression of kinase activity using the homogeneous time-resolved fluorescence assay versus epidermal growth factor receptor (EGFRWT) and EGFR790M. With IC50 values of 0.28 ± 0.03 and 5.02 ± 0.19, compound 2 was demonstrated to be the most effective against both forms of EGFR. Furthermore, compound 2 also had the best antioxidant property, decreasing the radical scavenging activity by 78%. Molecular docking research, on the other hand, was carried out for the analyzed candidates (1–7) to study their mechanism of action as EGFR inhibitors. In silico absorption, distribution, metabolism, excretion, and toxicity tests were also performed to explain the physicochemical features of the examined derivatives