title: Design, synthesis and biological evaluation of 1,3,6-trisubstituted β-carboline derivatives for cytotoxic and anti-leishmanial potential.
abstract: In the present study, 23 derivatives of 1,3,6-trisubstituted β-carboline were synthesized and evaluated for cytotoxic potential against four human cancer cells, namely A-549, HeLa, Hep G2 and MCF-7 as well as anti-leishmanial activity against Leishmania donovani (MHOM/80/IN/Dd8) promastigotes. Among the studied compounds, compounds 13c and 13q showed potent cytotoxic activity better than the parent compound 10. For instance, compound 13c was found to be the most cytotoxic with IC50 of 4.72, 3.59, 3.65 and 4.17 μM against A-549, HeLa, Hep G2 and MCF-7 respectively, while for compound 13q, IC50 were 15.47, 5.30, 6.15 and 13.39 μM against the same cancer cells respectively. Further, these two compounds were found to be apoptotic in A-549 and MCF-7 cells when observed using Annexin V/propidium iodide staining under confocal microscope. All the compounds were also tested for anti-leishmanial potential. In which, compounds 13u and 13c were found to show moderate inhibition with IC50 of 23.5±9.0 and 68.0±0.0 μM respectively, while compound 10 was the most active with IC50 of 9.0±2.8 μM, suggesting the modification at C-6 detrimental for anti-leishmanial activity. Interestingly, amongst all, compound 13c was found to be the most active for cytotoxic and moderately active for anti-leishmanial activity which can be further developed as a lead for these disease areas.
authors.affiliation: Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India.
authors.forename: Nitin A
authors.initials: NA
authors.lastname: Lunagariya
authors.affiliation: Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India.
authors.forename: Vikrantsinh M
authors.initials: VM
authors.lastname: Gohil
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India.
authors.forename: Varun
authors.initials: V
authors.lastname: Kushwah
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India.
authors.forename: Soumya
authors.initials: S
authors.lastname: Neelagiri
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India.
authors.forename: Sanyog
authors.initials: S
authors.lastname: Jain
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India.
authors.forename: Sushma
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India. Electronic address: kkbhutani@niper.ac.in.
authors.forename: Kamlesh K
authors.initials: KK
authors.lastname: Bhutani
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D013329:Structure-Activity Relationship
chemical_list: D000981:Antiprotozoal Agents; D002243:Carbolines
keywords: 1,3,6-Trisubstituted β-carboline; Anti-leishmanial; Apoptosis; Cancer; Cytotoxic