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

• Published in: European journal of medicinal chemistry Vol. 154; pp. 172 - 181
• Main Authors: Upadhyay, Akanksha, Kushwaha, Pragati, Gupta, Sampa, Dodda, Ranga Prasad, Ramalingam, Karthik, Kant, Ruchir, Goyal, Neena, Sashidhara, Koneni V.
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 25.06.2018; Elsevier
• Subjects: Chemistry, Medicinal; Leishmaniasis; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Pharmacophore hybridization; Science & Technology; Triazolyl 2-methyl-4-phenylquinoline-3-carboxylate; Triazolyl 2-methyl-4-phenylquinoline-3-carboxylate; Pharmacophore hybridization; Leishmaniasis; ACID; VIVO; GLYCOGEN-PHOSPHORYLASE; MIMICS; SAR; 1,2,3-TRIAZOLES; INHIBITORY-ACTIVITY
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2018.05.014

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. [Display omitted] •Novel triazolylquinoline derivatives were designed and synthesized.•Few compounds showed inhibitory activities against promastigote and intracellular amastigotes.•Compound 11u showed consistent activity up to day 28 post-treatment.•Most compounds follow the Lipinski “rule of five” criteria.