title: Synthesis and biological evaluation of caracasine acid derivatives.
abstract: A series of caracasine acid (1) derivatives were synthesized and evaluated for their in vitro cytotoxicity on human cancer-derived cell lines MCF-7 and PC-3, as well as for other activities such as antibacterial, antileishmanial and antitrypanosomal activity. Compound 1 was more effective than any of its derivatives against tested human cancer cell lines. PC-3 cells were more sensitive than MCF-7 to all compounds, particularly the methyl ester (2), the amide (9) and the epoxide (10). The evaluation of antiparasitic activity revealed that ester derivatives (2-8) and the amide derivative (9) were the most effective antileishmanial and antitrypanosomal compounds, even though their effect on Trypanosoma cruzi was modest. Finally, compound 1 and the derivatives evidenced a broad spectrum of antibacterial activity, as assayed against Gram-positive and Gram-negative bacteria.
authors.affiliation: Facultad de Farmacia, Universidad Central de Venezuela, Apartado 47206, Los Chaguaramos 1041-A, Caracas, Venezuela. Electronic address: katiuska.chavez@ucv.ve.
authors.forename: Katiuska
authors.initials: K
authors.lastname: Chávez
authors.affiliation: Escuela de Química, Facultad de Ciencias, Universidad Central de Venezuela, Apartado 47058, Los Chaguaramos 1041-A, Caracas, Venezuela.
authors.forename: Reinaldo S
authors.initials: RS
authors.lastname: Compagnone
authors.affiliation: Laboratorio de Genómica y Proteómica, Centro de Biotecnología, Fundación IDEA, Sartenejas, Baruta, Apartado 89000, Caracas 1080-A, Venezuela.
authors.forename: Annamil
authors.initials: A
authors.lastname: Álvarez
authors.affiliation: Laboratorio de Genómica y Proteómica, Centro de Biotecnología, Fundación IDEA, Sartenejas, Baruta, Apartado 89000, Caracas 1080-A, Venezuela.
authors.forename: Katherine
authors.initials: K
authors.lastname: Figarella
authors.affiliation: Laboratorio de Genómica y Proteómica, Centro de Biotecnología, Fundación IDEA, Sartenejas, Baruta, Apartado 89000, Caracas 1080-A, Venezuela.
authors.forename: Iván
authors.initials: I
authors.lastname: Galindo-Castro
authors.affiliation: Laboratorio de Genómica y Proteómica, Centro de Biotecnología, Fundación IDEA, Sartenejas, Baruta, Apartado 89000, Caracas 1080-A, Venezuela.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Marsiccobetre
authors.affiliation: Laboratorio de Genómica y Proteómica, Centro de Biotecnología, Fundación IDEA, Sartenejas, Baruta, Apartado 89000, Caracas 1080-A, Venezuela.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Triviño
authors.affiliation: Laboratorio de Genómica y Proteómica, Centro de Biotecnología, Fundación IDEA, Sartenejas, Baruta, Apartado 89000, Caracas 1080-A, Venezuela.
authors.forename: Irina
authors.initials: I
authors.lastname: Arocha
authors.affiliation: Universidad Simón Bolívar, Sartenejas, Baruta, Apartado 89000, Caracas 1080-A, Venezuela.
authors.forename: Antonieta
authors.initials: A
authors.lastname: Taddei
authors.affiliation: Facultad de Farmacia, Universidad Central de Venezuela, Apartado 47206, Los Chaguaramos 1041-A, Caracas, Venezuela.
authors.forename: Giovannina
authors.initials: G
authors.lastname: Orsini
authors.affiliation: Facultad de Farmacia, Universidad Central de Venezuela, Apartado 47206, Los Chaguaramos 1041-A, Caracas, Venezuela.
authors.forename: Stephen
authors.initials: S
authors.lastname: Tillett
authors.affiliation: Facultad de Farmacia, Universidad Central de Venezuela, Apartado 47206, Los Chaguaramos 1041-A, Caracas, Venezuela.
authors.forename: Alírica I
authors.initials: AI
authors.lastname: Suárez
mesh_terms: D000577:Amides / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001409:Bacillus cereus / Q000187:drug effects / Q000254:growth & development; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004852:Epoxy Compounds / Q000737:chemistry; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D004952:Esters / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D007894:Leishmania mexicana / Q000187:drug effects / Q000254:growth & development; D061986:MCF-7 Cells; D010616:Phenanthrenes / Q000138:chemical synthesis* / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013329:Structure-Activity Relationship; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000254:growth & development
chemical_list: D000577:Amides; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D000981:Antiprotozoal Agents; D002264:Carboxylic Acids; D004852:Epoxy Compounds; D004952:Esters; D010616:Phenanthrenes
keywords: Antibacterial; Antileishmanial; Antitrypanosomal; Caracasine acid; Cytotoxic activity; Ent-kaurane; Synthesis