title: Identification of a diverse indole-2-carboxamides as a potent antileishmanial chemotypes.
abstract: A novel series of highly diverse indole-2-carboxamides was synthesized utilizing the isocyanide based multicomponent reaction (IMCR)-post modification approach and were identified as potential antileishmanial chemotype. Among the synthesized 18 analogues, 12 analogues exhibited better antileishmanial activity against intracellular amastigotes form of Leishmania donovani (IC50 values of 0.6-7.5 μM) as compared to standard drugs miltefosine and sodium stibogluconate. The compounds were also non-toxic towards Vero cells. Compounds 2b, 2m and 2p with significant in vitro activity were then evaluated for their in vivo efficacy following intraperitoneal route. These three compounds at a concentration of 50 mg/kg/day for 5 consecutive days showed 70.0, 63.5 and 63.4% inhibition of Leishmania amastigotes, respectively at day 7 post treatment in hamster model of visceral leishmaniasis.
authors: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, U.P., India.
authors: Shashi
authors: S
authors: Pandey
authors: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, U.P., India.
authors: Shikha S
authors: SS
authors: Chauhan
authors: Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow 226031, U.P., India.
authors: Rahul
authors: R
authors: Shivahare
authors: Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Lucknow 226031, U.P., India; Academy of Scientific and Innovative Research, New Delhi, India.
authors: Abhisheak
authors: A
authors: Sharma
authors: Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Lucknow 226031, U.P., India; Academy of Scientific and Innovative Research, New Delhi, India.
authors: Swati
authors: S
authors: Jaiswal
authors: Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow 226031, U.P., India.
authors: Suman
authors: S
authors: Gupta
authors: Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Lucknow 226031, U.P., India; Academy of Scientific and Innovative Research, New Delhi, India.
authors: Jawahar
authors: J
authors: Lal
authors: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, U.P., India. Electronic address: prem_chauhan_2000@yahoo.com.
authors: Prem M S
authors: PM
authors: Chauhan
mesh_terms: D000577:Amides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D007893:Leishmania donovani / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008297:Male; D051379:Mice; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000577:Amides; D000981:Antiprotozoal Agents; D007211:Indoles
keywords: Hamster model; Indole-2-carboxamide; Leishmania donovani; Multicomponent reaction