title: Natural product-based synthesis of novel anti-infective isothiocyanate- and isoselenocyanate-functionalized amphilectane diterpenes.
abstract: The marine natural product (-)-8,15-diisocyano-11(20)-amphilectene (1), isolated from the Caribbean sponge Svenzea flava, was used as scaffold to synthetize five new products, all of which were tested against laboratory strains of Plasmodium falciparum and Mycobacterium tuberculosis H37Rv. The scaffold contains two isocyanide units that are amenable to chemical manipulation, enabling them to be elaborated into a small library of sulfur and selenium compounds. Although most of the analogs prepared were less potent than the parent compound, 5 was nearly equipotent showing IC50 values of 0.0066 μM and 0.0025 μM, respectively, against two strains (Dd2 and 3D7) of the malaria parasite. On the other hand, when assayed against the tuberculosis bacterium, analogs 5 and 6 were found to be more potent than 1.
authors.affiliation: Molecular Sciences Research Center, University of Puerto Rico, 1390 Ponce de León Avenue, San Juan, PR 00926, United States.
authors.forename: Karinel
authors.initials: K
authors.lastname: Nieves
authors.affiliation: Department of Cell Biology and Neuroscience, University of California at Riverside, CA 92521, United States.
authors.forename: Jacques
authors.initials: J
authors.lastname: Prudhomme
authors.affiliation: Department of Cell Biology and Neuroscience, University of California at Riverside, CA 92521, United States.
authors.forename: Karine G
authors.initials: KG
authors.lastname: Le Roch
authors.affiliation: Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, United States.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Franzblau
authors.affiliation: Molecular Sciences Research Center, University of Puerto Rico, 1390 Ponce de León Avenue, San Juan, PR 00926, United States. Electronic address: abimael.rodriguez1@upr.edu.
authors.forename: Abimael D
authors.initials: AD
authors.lastname: Rodríguez
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry*; D003485:Cyanates / Q000737:chemistry*; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D017879:Isothiocyanates / Q000737:chemistry*; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects; D011161:Porifera / Q000737:chemistry / Q000378:metabolism; D018036:Selenium Compounds / Q000737:chemistry*
chemical_list: D000890:Anti-Infective Agents; D001688:Biological Products; D003485:Cyanates; D004224:Diterpenes; D017879:Isothiocyanates; D018036:Selenium Compounds; C037152:isothiocyanic acid; C053721:selenocyanic acid
keywords: Isocyanide; Isoselenocyanate; Isothiocyanate; Malaria; Synthesis of natural product derivatives; Tuberculosis