Antileishmanial ferrocenylquinoline derivatives: Synthesis and biological evaluation against Leishmania donovani.
The emergence of resistance against existing antileishmanial drugs necessitates the search for new classes of antileishmanial compounds. Herein a series of structurally diverse ferrocenylquinolines have been synthesized and evaluated for in vitro antileishmanial activity against Leishmania donovani using the MTT assay. Thirteen (M2-M14) substituted ferrocenylquinoline congeners possessing triazole rings were generated by palladium mediated Suzuki-Miyaura coupling reaction of 5-iodoferrocenylquinolinetriazole and substituted arylboronic acids. All the synthesized compounds were tested for its antileishmanial activity using both promastigote and amastigote stages of L. donovani. Among them, three compounds (M4, M7 and M9) exhibited promising anti-promastigote activity, with an IC50value of 28.7 μM, 22.1 μM and 28 μM, respectively, and no cytotoxicity toward host splenocytes. These three compounds are equally effective against the intracellular amastigote stage of L. donovani showing the IC50values of 16 μM (M4), 8 μM (M7) and 16 μM (M9), respectively, with consistent nitric oxide generation as required for parasite clearance. From the battery of tests conducted in this study, it appears that these compounds induce parasite death by promoting cell cycle arrest and triggering apoptosis.
Department of Chemistry, University of Calcutta, 92, A.P.C. Road, Kolkata, 700 009, India.
Md
M
Yousuf
Cellular Immunology and Experimental Therapeutics Laboratory, Department of Zoology, West Bengal State University, Barasat, West Bengal, India.
Debarati
D
Mukherjee
Cellular Immunology and Experimental Therapeutics Laboratory, Department of Zoology, West Bengal State University, Barasat, West Bengal, India.
Somaditya
S
Dey
Cellular Immunology and Experimental Therapeutics Laboratory, Department of Zoology, West Bengal State University, Barasat, West Bengal, India.
Chiranjib
C
Pal
Department of Chemistry, University of Calcutta, 92, A.P.C. Road, Kolkata, 700 009, India. Electronic address: adhikarisusanta@yahoo.com.
Susanta
S
Adhikari
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects*; D051379:Mice; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013154:Spleen / Q000166:cytology; D013329:Structure-Activity Relationship
D000981:Antiprotozoal Agents; D011804:Quinolines
1,2,3-Triazole; Apoptosis; Leishmania donovani; Metallocene; Nitric oxide; Suzuki-Miyaura coupling