title: Novel capsaicin analogues as potential anticancer agents: synthesis, biological evaluation, and in silico approach.
abstract: A novel class of benzo[d][1,3]dioxol-5-ylmethyl alkyl/aryl amide and ester analogues of capsaicin were designed, synthesized, and evaluated for their cytotoxic activity against human and murine cancer cell lines (B16F10, SK-MEL-28, NCI-H1299, NCI-H460, SK-BR-3, and MDA-MB-231) and human lung fibroblasts (MRC-5). Three compounds (5f, 6c, and 6e) selectively inhibited the growth of aggressive cancer cells in the micromolar (µM) range. Furthermore, an exploratory data analysis pointed at the topological and electronic molecular properties as responsible for the discrimination process regarding the set of investigated compounds. The findings suggest that the applied designing strategy, besides providing more potent analogues, indicates the aryl amides and esters as well as the alkyl esters as interesting scaffolds to design and develop novel anticancer agents.
authors.affiliation: Department of Pharmacy, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Mariana C F C B
authors.initials: MC
authors.lastname: Damião
authors.forename: Kerly F M
authors.initials: KF
authors.lastname: Pasqualoto
authors.forename: Adilson K
authors.initials: AK
authors.lastname: Ferreira
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Teixeira
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Azevedo
authors.forename: José A M
authors.initials: JA
authors.lastname: Barbuto
authors.forename: Fanny
authors.initials: F
authors.lastname: Palace-Berl
authors.forename: Gilberto C
authors.initials: GC
authors.lastname: Franchi-Junior
authors.forename: Alexandre E
authors.initials: AE
authors.lastname: Nowill
authors.forename: Maurício T
authors.initials: MT
authors.lastname: Tavares
authors.forename: Roberto
authors.initials: R
authors.lastname: Parise-Filho
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002211:Capsaicin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016000:Cluster Analysis; D017076:Computer-Aided Design; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D025341:Principal Component Analysis; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002211:Capsaicin
keywords: Bioisosterism; Capsaicin analogues; Cytotoxic activity; Exploratory data analysis; Molecular modification