Novel Capsaicin Analogues as Potential Anticancer Agents: Synthesis, Biological Evaluation, and In Silico Approach

被引：17

作者：

Damiao, Mariana C. F. C. B. ^{[1
]}

Pasqualoto, Kerly F. M. ^{[2
]}

Ferreira, Adilson K. ^{[3
]}

Teixeira, Sarah F. ^{[3
]}

Azevedo, Ricardo A. ^{[3
]}

Barbuto, Jose A. M. ^{[3
,4
]}

Palace-Berl, Fanny ^{[5
]}

Franchi-Junior, Gilberto C. ^{[6
]}

Nowill, Alexandre E. ^{[6
]}

Tavares, Mauricio T. ^{[1
]}

Parise-Filho, Roberto ^{[1
]}

机构：

[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Pharm, BR-05508000 Sao Paulo, Brazil

[2] Butantan Inst, Biochem & Biophys Lab, Sao Paulo, Brazil

[3] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Lab Tumor Immunol, BR-05508000 Sao Paulo, Brazil

[4] Univ Sao Paulo, Fac Med, Cell & Mol Therapy Ctr NUCEL NETCEM, BR-05508000 Sao Paulo, Brazil

[5] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Biochem Pharmaceut Technol, BR-05508000 Sao Paulo, Brazil

[6] Univ Estadual Campinas, Fac Med Sci, Oncohematol Child Res Ctr, Campinas, SP, Brazil

来源：

ARCHIV DER PHARMAZIE | 2014年 / 347卷 / 12期

关键词：

Bioisosterism; Capsaicin analogues; Cytotoxic activity; Exploratory data analysis; Molecular modification; CELL-CYCLE ARREST; QUANTITATIVE STRUCTURE; APOPTOSIS; DERIVATIVES; PREDICTION; INHIBITORS;

D O I：

10.1002/ardp.201400233

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 (mM) 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.

引用

页码：885 / 895

页数：11

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