title: Synthesis, structure-activity relationships, and biological studies of chromenochalcones as potential antileishmanial agents.
abstract: Antileishmanial activities of a library of synthetic chalcone analogues have been examined. Among them, five compounds (11, 14, 16, 17, 22, and 24) exhibited better activity than the marketed drug miltefosine in in vitro studies against the intracellular amastigotes form of Leishmania donovani. Three promising compounds, 16, 17, and 22, were tested in a L. donovani/hamster model. Oral administration of chalcone 16, at a concentration of 100 mg/kg of body weight per day for 5 consecutive days, resulted in >84% parasite inhibition at day 7 post-treatment and it retained the activity until day 28. The molecular and immunological studies revealed that compound 16 has a dual nature to act as a direct parasite killing agent and as a host immunostimulant. Pharmacokinetics and serum albumin binding studies also suggest that compound 16 has the potential to be a candidate for the treatment of the nonhealing form of leishmaniasis.
authors.affiliation: Division of Parasitology, CSIR-Central Drug Research Institute , Lucknow 226 031, Uttar Pradesh, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Shivahare
authors.forename: Venkateswarlu
authors.initials: V
authors.lastname: Korthikunta
authors.forename: Hardik
authors.initials: H
authors.lastname: Chandasana
authors.forename: Manish K
authors.initials: MK
authors.lastname: Suthar
authors.forename: Pragati
authors.initials: P
authors.lastname: Agnihotri
authors.forename: Preeti
authors.initials: P
authors.lastname: Vishwakarma
authors.forename: Telaprolu K
authors.initials: TK
authors.lastname: Chaitanya
authors.forename: Papireddy
authors.initials: P
authors.lastname: Kancharla
authors.forename: Tanvir
authors.initials: T
authors.lastname: Khaliq
authors.forename: Shweta
authors.initials: S
authors.lastname: Gupta
authors.forename: Rabi Sankar
authors.initials: RS
authors.lastname: Bhatta
authors.forename: J Venkatesh
authors.initials: JV
authors.lastname: Pratap
authors.forename: Jitendra K
authors.initials: JK
authors.lastname: Saxena
authors.forename: Suman
authors.initials: S
authors.lastname: Gupta
authors.forename: Narender
authors.initials: N
authors.lastname: Tadigoppula
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D047188:Chalcones / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D006224:Cricetinae; D016207:Cytokines / Q000096:biosynthesis; D004355:Drug Stability; D007893:Leishmania donovani / Q000187:drug effects*; D008264:Macrophages / Q000276:immunology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008647:Mesocricetus; D009569:Nitric Oxide / Q000096:biosynthesis; D013329:Structure-Activity Relationship
chemical_list: D000981:Antiprotozoal Agents; D047188:Chalcones; D016207:Cytokines; D009569:Nitric Oxide