title: Synthesis, antileishmanial and antitrypanosomal activities of N-substituted tetrahydro-β-carbolines.
abstract: A series of N-substituted tetrahydro-β-carbolines were synthesized and screened for antileishmanial activity through an in vitro assay that involves promastigotes and axenic amastigotes of Leishmania donovani, the causative agent for visceral leishmaniasis. The thiophen-2-yl analogs 9b and 11f and naphthyl analog 11h were found to show significant activity against promastigotes with IC50 values of 12.7, 9.1 and 22.1 μM, respectively. Analogs 9b and 11h were also effective against axenic amastigotes with IC50 values of 62.8 and 87.6 μM, respectively. The antileishmanial activity of analogs was then tested in human macrophage cell line infected with L. donovani amastigotes and 2-naphthyl linked analog 11h was found to be effective with IC50 value of 28.3 μM. Several analogs also displayed antitrypanosomal activity against Trypanosoma brucei, the causative agent for human African trypanosomiasis. Compounds 11e, 11f and 11h were more effective than others with IC50 values of 1.0, 8.9 and 10.2 μM, respectively. All synthesized analogs were not cytotoxic towards mammalian cell lines including Vero (monkey kidney fibroblasts), HEPG2 (human hepatoma cells), LLC-PK1 (pig kidney epithelial cells) and THP-1 (human macrophages).
authors: Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; Academy of Scientific & Innovative Research (AcSIR), CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors: Sudhakar
authors: S
authors: Manda
authors: National Center for Natural Products Research (NCNPR), School of Pharmacy, University of Mississippi, MS 38677, USA.
authors: Shabana I
authors: SI
authors: Khan
authors: National Center for Natural Products Research (NCNPR), School of Pharmacy, University of Mississippi, MS 38677, USA.
authors: Surendra K
authors: SK
authors: Jain
authors: Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; Academy of Scientific & Innovative Research (AcSIR), CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors: Shabber
authors: S
authors: Mohammed
authors: National Center for Natural Products Research (NCNPR), School of Pharmacy, University of Mississippi, MS 38677, USA.
authors: Babu L
authors: BL
authors: Tekwani
authors: National Center for Natural Products Research (NCNPR), School of Pharmacy, University of Mississippi, MS 38677, USA.
authors: Ikhlas A
authors: IA
authors: Khan
authors: Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; Academy of Scientific & Innovative Research (AcSIR), CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India. Electronic address: ram@iiim.res.in.
authors: Ram A
authors: RA
authors: Vishwakarma
authors: Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; Academy of Scientific & Innovative Research (AcSIR), CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India. Electronic address: sbharate@iiim.res.in.
authors: Sandip B
authors: SB
authors: Bharate
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship; D013552:Swine; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014709:Vero Cells
chemical_list: D000981:Antiprotozoal Agents; D002243:Carbolines
keywords: African trypanosomiasis; Antileishmanial; Antitrypanosomal; Leishmania donovani; Leishmaniasis; Tetrahydro-β-carbolines