ABSTRACT
Aim: To synthesize and screen phenanthridine and 1,2,3-triazole derivatives for antileishmanial activity. Methodology: Synthesized analogs were tested for antileishmanial activity against transgenic strain of Leishmania infantum promastigotes and ex vivo infections. Results: Compounds T01, T08 and T11 revealed significant activity with EC50 <30 µm and lacked toxicity in mouse spleen and HepG2 cells. T01 with EC50 3.07 µm is fourfold more potent than the drug miltefosine (EC50 12.6 µM) against L. infantum promastigotes. In silico studies indicate that the analogs are nontoxic. A molecular docking analysis was also carried out on the T01 and T08 to investigate the binding pattern at the active site of the chosen target trypanothione reductase. Conclusion: The results of this study reveal that phenanthridine triazoles exhibit antileishmanial activity.
Subject(s)
Antiprotozoal Agents , Leishmania infantum , Animals , Antiprotozoal Agents/chemistry , Mice , Molecular Docking Simulation , Phenanthridines/pharmacology , Triazoles/pharmacologyABSTRACT
Aim: Literature reports suggest spirochromanone derivatives exhibit anticancer activity. Methodology: The authors designed and synthesized 18 spirochromanone derivatives (Csp 1-18). The compounds were characterized and evaluated for anticancer activity against human breast cancer (MCF-7) and murine melanoma (B16F10) cell lines. Results: The anticancer activity ranged from 4.34 to 29.31 µm. The most potent compounds, Csp 12 and Csp 18, were less toxic against the human embryonic kidney (HEK-293) cell line and â¼ two/â¼fourfold selective toward MCF-7 than B16F10 in comparison to the reference, BG-45. Csp 12 caused 28.6% total apoptosis, leading to significant cytotoxicity, and arrested the G2 phase of the cell cycle in B16F10 cells. A molecular docking study of Csp 12 exhibited effective binding at the active site of the epidermal growth factor receptor kinase domain. Conclusion: This study highlights the importance of spirochromanones as anticancer agents.
Subject(s)
Antineoplastic Agents/chemical synthesis , Chromans/chemistry , Drug Design , Spiro Compounds/chemistry , Animals , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Binding Sites , Catalytic Domain , Cell Line, Tumor , Chromans/metabolism , Chromans/pharmacology , Drug Screening Assays, Antitumor , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , G2 Phase Cell Cycle Checkpoints/drug effects , Humans , Mice , Molecular Docking Simulation , Structure-Activity RelationshipABSTRACT
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.
