title: Chemotherapy of leishmaniasis. Part IX: synthesis and bioevaluation of aryl substituted ketene dithioacetals as antileishmanial agents.
abstract: A new series of aryl substituted ketene dithioacetals 6a-h was synthesized and evaluated for their in vitro and in vivo antileishmanial activity against Leishmania donovani. Two compounds exhibited significant in vitro activity against intracellular amastigotes of L. donovani with IC(50) values 3.56 and 5.12 μM and were found promising as compared with reference drug, miltefosine. On the basis of good Selectivity Indices (S.I.), they were further tested for their in vivo response against L. donovani/hamster model and showed significant inhibition of parasite multiplication 78% and 83%, respectively. These compounds were better than the existing antileishmanials in respect to IC(50) and SI values, but were less active than miltefosine in vivo.
authors.affiliation: Division of Medicinal Chemistry, Central Drug Research Institute, CSIR, Lucknow 226001, India.
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumar
authors.forename: Avinash
authors.initials: A
authors.lastname: Tiwari
authors.forename: S N
authors.initials: SN
authors.lastname: Suryawanshi
authors.forename: Monika
authors.initials: M
authors.lastname: Mittal
authors.forename: Preeti
authors.initials: P
authors.lastname: Vishwakarma
authors.forename: Suman
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000080:Acetals / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006224:Cricetinae; D005030:Ethylenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007893:Leishmania donovani / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy*; D023421:Models, Animal; D015394:Molecular Structure; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000080:Acetals; D000981:Antiprotozoal Agents; D005030:Ethylenes; D007659:Ketones; D013438:Sulfhydryl Compounds; D010767:Phosphorylcholine; C039128:miltefosine; C008223:ketene