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.

Oxidant-based anticancer activity of a novel synthetic analogue of capsaicin, capsaicin epoxide

“…21,22 The experimental data on the capsaicin chemical modification-mediated cytotoxic potential against cancer cells are limited. 23,24 A previous study found that the RPF101 capsaicin-like analogue exhibits higher antitumour activity than capsaicin by inducing arrest of the cell cycle at the G2/M phase through disruption of the microtubule network in MCF7 cells. 23 Piperonylamine was sulfonylated by benzenesulfonyl chloride to yield RPF101 with more suitable lipophilic properties and a hydrogen bond acceptor character, which are relevant features for improved pharmacokinetic and pharmacodynamic profiles.…”

Anticancer Activity of Natural and Synthetic Capsaicin Analogs

“…7C) displayed potent growth-suppressive activity in TRPV1-OE cells, and this process was mediated by the ROS oxidative stress pathway (Thomas et al, 2007). Damião et al (2014) synthesized a variety of capsaicin analogs (Fig. 7, C-E) and tested for their cytotoxicity in B16F10 (mouse melanoma), SK-MEL-28 (human melanoma), NCI-H1299, NCI-H460 (human lung cancer), SK-BR-3, and MDA-MB-231 (human breast cancers) cell lines (Damião et al, 2014).…”

Avaliação da atividade do CHY-1, um novo análogo da miltefosina, como potencial inibidor da enzima CTP: fosfoetanolamina-citidilil-transferase, sobre o carcinoma de pulmão de não-pequenas células.

“…A indução da exposição de calreticulina por CHY-1 . DAMIÃO et al, 2014;OVERINGTON;NARANG;DESAI, 2009;PALACE-BERL et al, 2015;TEIXEIRA et al, 2014). Neste contexto os fosfolipídios e as vias de produção destes surgem como um ponto de interesse devido as suas funções celulares e à presença de alterações relacionadas a eles e suas funções no contexto tumoral (IGAL, 2010;MENENDEZ;LUPU, 2007;RYSMAN et al, 2010;SCOTT et al, 2010;SWINNEN et al, 2003).…”