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  • Novel capsaicin analogues as potential anticancer agents: synthesis, biological evaluation, and in silico approach.

Novel capsaicin analogues as potential anticancer agents: synthesis, biological evaluation, and in silico approach.

Archiv der Pharmazie (2014-10-07)
Mariana C F C B Damião, Kerly F M Pasqualoto, Adilson K Ferreira, Sarah F Teixeira, Ricardo A Azevedo, José A M Barbuto, Fanny Palace-Berl, Gilberto C Franchi-Junior, Alexandre E Nowill, Maurício T Tavares, Roberto Parise-Filho
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.

MATERIALS
Product Number
Brand
Product Description

Supelco
Capsaicin, analytical standard
Supelco
Melting point standard 182-184°C, analytical standard
Sigma-Aldrich
1,3-Propylene sulfite, 99%
Capsaicin, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Capsaicin, ≥95%, from Capsicum sp.
Sigma-Aldrich
Capsaicin, from Capsicum sp., ≥50% (HPLC)
Sigma-Aldrich
Hexanoic acid, purum, ≥98.0% (GC)
Supelco
Hexanoic acid, analytical standard
Supelco
Mettler-Toledo Calibration substance ME 18555, Benzoic acid, analytical standard, (for the calibration of the melting point system), traceable to primary standards (LGC)
Sigma-Aldrich
Hexanoic acid, ≥99%
Sigma-Aldrich
Oxalyl chloride, ReagentPlus®, ≥99%
Sigma-Aldrich
Capsaicin, natural
Sigma-Aldrich
p-Anisic acid, ≥99%, FG
Sigma-Aldrich
3-Nitrobenzoic acid, ReagentPlus®, 99%
Sigma-Aldrich
Hexanoic acid, ≥98%, FCC, FG
Sigma-Aldrich
Piperonyl alcohol, 98%
Sigma-Aldrich
Oxalyl chloride, reagent grade, 98%
Sigma-Aldrich
Piperonylamine, 97%
Sigma-Aldrich
p-Toluic acid, 98%
Supelco
Capsaicin, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Capsaicin, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Oxalyl chloride solution, 2.0 M in methylene chloride
Supelco
Melting point standard 121-123°C, analytical standard
Supelco
Benzoic acid, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Benzoic acid, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Benzoic acid, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥99.9% (alkalimetric)
Supelco
Benzoic acid, reference material for titrimetry, certified by BAM, >99.5%
Sigma-Aldrich
Benzoic acid, meets analytical specification of Ph. Eur., BP, USP, FCC, E210, 99.5-100.5% (alkalimetric)
Sigma-Aldrich
Isovaleric acid, ≥99%, FCC, FG
Sigma-Aldrich
Isovaleric acid, natural, ≥98%, FG