title: Synthesis of Unsymmetrical Sulfides and Their Oxidation to Sulfones to Discover Potent Antileishmanial Agents.
abstract: Unsymmetrical sulfides were first synthesized using combinations of a 1,3-dicarbonyl, an aromatic aldehyde and a thiol in the presence of 10 mol % ethanolic piperidine. These sulfides derivatives were subsequently converted into corresponding sulfones via oxidation in the presence of m-chloroperoxybenzoic acid (m-CPBA) at ice-bath to room temperature. The former reaction was achieved at room temperature through one-pot three-component. The later was obtained in good yields using mild reaction conditions with flexibility in choice from a range of substrates. The antimicrobial properties of the newly synthesized sulfone derivatives were investigated against the protozoan parasite, Leishmania donovani, a causative agent of visceral leishmaniasis (VL). Nine sulfone derivatives were found to be efficacious and exhibited significant antimicrobial activity. Further, these compounds were nontoxic on murine peritoneal macrophages thus eliminating potential cytoxicity in the host cells. These compounds may be indicated as potential leads in the treatment of visceral leishmaniasis.
authors.affiliation: Department of Chemistry, Indian Institute of Technology Guwahati , Guwahati 781 039, India.
authors.forename: Ajaz A
authors.initials: AA
authors.lastname: Dar
authors.affiliation: Department of Chemistry, Indian Institute of Technology Guwahati , Guwahati 781 039, India.
authors.forename: Nagasuresh
authors.initials: N
authors.lastname: Enjamuri
authors.forename: Md
authors.initials: M
authors.lastname: Shadab
authors.affiliation: Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology , 4, Raja S.C. Mullick Road, Kolkata 700 032, India.
authors.forename: Nahid
authors.initials: N
authors.lastname: Ali
authors.affiliation: Department of Chemistry, Indian Institute of Technology Guwahati , Guwahati 781 039, India.|Aliah University , IIA/27, New Town, Kolkata-700 156, West Bengal, India.
authors.forename: Abu T
authors.initials: AT
authors.lastname: Khan
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020650:Combinatorial Chemistry Techniques; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D013440:Sulfides; D013450:Sulfones
keywords: Knoevenagel-thia-Michael reaction; Leishmania donovani; m-chloroperoxybenzoic acid; protozoan parasite; sulfones; unsymmetrical sulfides (β-mercapto diketones); visceral leishmaniasis