In silico and in vitro investigation of anticancer effect of newly synthesized nonivamide-s-allyl cysteine ester

From Natural Sources to Synthetic Derivatives: The Allyl Motif as a Powerful Tool for Fragment-Based Design in Cancer Treatment

“…In a search for new anticancer molecules, molecule 12 containing noniv­amide ( 11 ), a less pungent analog of capsaicin and SAC ( 8 ), was developed (Figure ). Molecular docking studies and dynamics simulation analysis suggested the potential for a stable interaction and favorable binding of the hybrid molecule 12 with therapeutic target proteins that included the human estrogen receptor α (ER-α), tumor protein negative regulator mouse double minute 2 (MDM2), B-cell lymphoma 2 (Bcl-2), and cyclin-dependent kinase 2 (CDK2) to treat cancer . These molecular docking studies suggested that 12 could interact with ERα at a site similar to that of the antagonist tamoxifen.…”

“…Finally, it increased p53 expression and decreased the Bcl/Bax ratio. 22 Other SAC-derived hybrid compounds 13 – 15 were obtained by combining this fragment with non-steroidal anti-inflammatory drugs (NSAIDs), resulting in promising scaffolds for the treatment of colorectal cancer ( Figure 4 ). The IC 50 values for these hybrids at 24 and 48 h against colon adenocarcinoma SW480 cell line were between 0.131 and 0.183 mM, and selectivity indexes, calculated as the ratio of IC 50 values in non-malignant CHO-K1 cells versus SW480 cells, were higher than 1 after 48 h of treatment.…”

“…Molecular docking studies and dynamics simulation analysis suggested the potential for a stable interaction and favorable binding of the hybrid molecule 12 with therapeutic target proteins that included the human estrogen receptor α (ER-α), tumor protein negative regulator mouse double minute 2 (MDM2), B-cell lymphoma 2 (Bcl-2), and cyclin-dependent kinase 2 (CDK2) to treat cancer. 22 These molecular docking studies suggested that 12 could interact with ERα at a site similar to that of the antagonist tamoxifen. Similarly, MDM2 plays an important role in cancer, as it is a negative regulator of the nuclear transcription factor p53.…”

Functional Foods: Capcaisin And Receptor-independent ways

“…The synergetic effect of functional foods can be demonstrated by another natural compound S-allyl cysteine (SAC) and capsaicin, the less pungent capsaicin analogue Nonivamide (NOV), which is found in various Capsicum species. The synergistic effect of NOV-SAC may be with therapeutic target proteins for cancer treatment: human estrogen receptor α, tumor protein negative regulator mouse double min 2, B-cell lymphoma 2, and cyclindependent kinase 2 (22). Moreover, Capsaicin potently suppresses the growth of prostate carcinoma cells in vitro and in vivo.…”

Dithiol‐Activated Bioorthogonal Chemistry for Endoplasmic Reticulum‐Targeted Synergistic Chemophototherapy

“…Capsaicin and analogues (e.g., nonivamide) are potent agonists of the TRPV1 receptor, utilized to treat pain and inflammation [30] . Recently, several lines of studies reveal that capsaicin and nonivamide display strong antineoplastic activity in a wide array of human cancer cells via multiple mechanisms like induction of ROS and RNS, inhibition of NADH oxidase activity and mitochondrial respiration, and serious ER stress [31–33] . The pharmacological activity of capsaicin and nonivamide is highly dependent on its concentration in target tissues [34–36] .…”