title: Synthesis and biological evaluation of ferrocenylquinoline as a potential antileishmanial agent.
abstract: The emergence of resistance against antileishmanial drugs in current use necessitates the search for new classes of antileishmanial compounds. Herein we report the design, synthesis, and evaluation of a novel ferrocenylquinoline for activity against Leishmania donovani. 7-Chloro-N-[2-(1H-5-ferrocenyl-1,2,3-triazol-1-yl)ethyl]quinolin-4-amine (1) was generated by coupling an iron(II) ethynylferrocene species with 4-(2-ethylazido)amino-7-chloroquinoline using click chemistry. The synthesized compound 1 was tested for its antileishmanial activity using both promastigote and amastigote stages of L. donovani. Compound 1 showed promising anti-promastigote activity, with an IC50 value of 15.26 μM and no cytotoxicity toward host splenocytes. From the battery of tests conducted in this study, it appears that this compound induces parasite death by promoting oxidative stress and depolarizing the mitochondrial membrane potential, thereby triggering apoptosis. These results suggest that ferrocenylquinoline 1 is a suitable lead for the development of new antileishmanial drugs.
authors.affiliation: Department of Chemistry, University of Calcutta, 92 A.P.C. Road, Kolkata 700 009 (India).
authors.forename: Md
authors.initials: M
authors.lastname: Yousuf
authors.forename: Debarati
authors.initials: D
authors.lastname: Mukherjee
authors.forename: Abhishek
authors.initials: A
authors.lastname: Pal
authors.forename: Somaditya
authors.initials: S
authors.lastname: Dey
authors.forename: Supratim
authors.initials: S
authors.lastname: Mandal
authors.forename: Chiranjib
authors.initials: C
authors.lastname: Pal
authors.forename: Susanta
authors.initials: S
authors.lastname: Adhikari
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D057930:Click Chemistry; D005296:Ferrous Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000166:cytology / Q000187:drug effects*; D018320:Leishmania major / Q000166:cytology / Q000187:drug effects; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy; D007898:Leishmaniasis, Visceral / Q000188:drug therapy; D000075163:Metallocenes; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000981:Antiprotozoal Agents; D005296:Ferrous Compounds; D000075163:Metallocenes; D011804:Quinolines; C037219:quinoline; C004998:ferrocene
keywords: Leishmania donovani; apoptosis; click chemistry; ferrocenes; reactive oxygen species