Synthesis and evaluation of novel triazolyl quinoline derivatives as potential antileishmanial agents

  • Eur J Med Chem. 2018 Jun 25:154:172-181. doi: 10.1016/j.ejmech.2018.05.014.
Akanksha Upadhyay  1 ,  Pragati Kushwaha  1 ,  Sampa Gupta  1 ,  Ranga Prasad Dodda  1 ,  Karthik Ramalingam  2 ,  Ruchir Kant  3 ,  Neena Goyal  4 ,  Koneni V Sashidhara  5
Affiliations
  • 1. Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram extension, Sitapur Road, Lucknow, 226031, India.
  • 2. Division of Biochemistry, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram extension, Sitapur Road, Lucknow, 226031, India.
  • 3. Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram extension, Sitapur Road, Lucknow, 226031, India.
  • 4. Division of Biochemistry, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram extension, Sitapur Road, Lucknow, 226031, India. Electronic address: [email protected].
  • 5. Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram extension, Sitapur Road, Lucknow, 226031, India. Electronic address: [email protected].
PMID: 29793211 DOI: 10.1016/j.ejmech.2018.05.014
Abstract

The high potential of quinoline containing natural products and their derivatives in medicinal chemistry led us to discover novel series of 25 compounds for the development of new antileishmanial agents. A series of triazolyl 2-methyl-4-phenylquinoline-3-carboxylate derivatives has been synthesized via click chemistry inspired molecular hybridization approach and evaluated against Leishmania donovani. Most of the screened derivatives exhibited significant in vitro anti-leishmanial activity against promastigote (IC50 ranging from 2.43 to 45.75 μM) and intracellular amastigotes (IC50 ranging from 7.06 to 34.9 μM) than the control, miltefosine (IC50 = 8.4 μM), with less cytotoxicity in comparison to the standard drugs. Overall results revealed that prototype signify a new structural lead for antileishmanial chemotherapy.

Keywords
Leishmaniasis; Pharmacophore hybridization; Triazolyl 2-methyl-4-phenylquinoline-3-carboxylate.