Design, synthesis, and biological evaluation of novel quinoxaline aryl ethers as anticancer agents.

We designed and synthesized thirty novel quinoxaline aryl ethers as anticancer agents, and the structures of final compounds were confirmed with various analytical techniques like Mass, 1 H NMR, 13 C NMR, FTIR, and elemental analyses. The compounds were tested against three cancer cell lines: colon cancer (HCT-116), breast cancer (MDA-MB-231), prostate cancer (DU-145), and one normal cell line: human embryonic kidney cell line (HEK-293). The obtained results indicate that two compounds, FQ and MQ, with IC50 values < 16 µM, were the most active compounds. Molecular docking studies revealed the binding of FQ and MQ molecules in the active site of the c-Met kinase (PDB ID: 3F66, 1.40 Å). Furthermore, QikProp ADME prediction and the MDS analysis preserved those critical docking data of both compounds, FQ and MQ. Western blotting was used to confirm the impact of the compounds FQ and MQ on the inhibition of the c-Met kinase receptor. The apoptosis assays were performed to investigate the mechanism of cell death for the most active compounds, FQ and MQ. The Annexin V/7-AAD assay indicated apoptosis in MDA-MB-231 cells treated with FQ and MQ, with FQ (21.4%) showing a higher efficacy in killing MDA-MB-231 cells than MQ (14.25%). The Caspase 3/7 7-AAD assay further supported these findings, revealing higher percentages of apoptotic cells for FQ-treated MDA-MB-231 cells (41.8%). The results obtained from the apoptosis assay conclude that FQ exhibits better anticancer activity against MDA-MB-231 cells than MQ.

Recent evolution on synthesis strategies and anti-leishmanial activity of ß-carboline derivatives - An update.

Leishmaniasis is the most widespread pathogenic disease in several countries. Currently, no effective vaccines are available, and the control of Leishmaniasis primarily relies on decade-old chemotherapy. The treatment for the Leishmaniasis is not up to the mark. Current therapy for Leishmaniasis is ancient and requires hospitalization for the administration. These medications are also highly toxic and resistant. ß-carboline, a natural indole containing alkaloid, holds a vital position in the field of medicinal chemistry with a diversified pharmacological action. The current review focuses mainly on the anti-leishmanial effects of ß-carboline analogs and their synthetic strategies, structural activity relationship studies (SAR). The past ten years alterations unveiled by ß-carboline analogs present in phytoconstituents and various derivatives of synthesized analogs with the mechanism of action were briefly shortlisted and illustrated.