Phase transfer catalyzed synthesis of bis-quinolines: antileishmanial activity in experimental visceral leishmaniasis and in vitro antibacterial evaluation.
A one-pot synthesis of some novel bis-quinolines has been achieved under phase transfer catalyzed conditions using 8-hydroxy quinoline derivatives as substrates. The synthesized analogues were evaluated for antileishmanial activity against Leishmania donovani promastigotes and amastigotes. The entire bis-quinolines showed efficacy in both in vitro and in vivo studies. Compound 5 (1,1-bis-[(5-chloro-8-quinolyl)oxy]methane) exhibited the most significant activity. Compounds 4 (1,1-bis-[(8-quinolyl)oxy]methane) and 9 (1,5-bis-[(2-methyl-8-quinolyl)oxy]pentane) also demonstrated significant leishmanicidal efficacy against established visceral leishmaniasis in BALB/c model. Ultrastructural studies of promastigotes treated with compound 5, demonstrated membrane blebbing, chromatin condensation and vacuolization in the parasites and the flagellated parasites became round shaped after treatment. Moreover, in vitro antibacterial activity of compound 5 against several bacterial strains revealed its promising efficacy. The findings suggested that 1,1-bis-[(5-chloro-8-quinolyl)oxy]methane (5) is a bright candidate to be considered as lead compound for leishmanicidal drug.
Steroid and Terpenoid Chemistry Division, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, 4 Raja SC Mullick Road, Jadavpur, Kolkata 700032, India.
Partha
P
Palit
Priyankar
P
Paira
Abhijit
A
Hazra
Sukdeb
S
Banerjee
Asish Das
AD
Gupta
Sujata G
SG
Dastidar
Nirup B
NB
Mondal
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D000981:Antiprotozoal Agents / Q000737:chemistry*; D002384:Catalysis; D007893:Leishmania donovani / Q000187:drug effects; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D021261:Parasitic Sensitivity Tests; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000981:Antiprotozoal Agents; D011804:Quinolines