Molecular Modeling and In Vitro Evaluation of Piplartine Analogs against Oral Squamous Cell Carcinoma.

Cancer is a principal cause of death in the world, and providing a better quality of life and reducing mortality through effective pharmacological treatment remains a challenge. Among malignant tumor types, squamous cell carcinoma-esophageal cancer (EC) is usually located in the mouth, with approximately 90% located mainly on the tongue and floor of the mouth. Piplartine is an alkamide found in certain species of the genus Piper and presents many pharmacological properties including antitumor activity. In the present study, the cytotoxic potential of a collection of piplartine analogs against human oral SCC9 carcinoma cells was evaluated. The analogs were prepared via Fischer esterification reactions, alkyl and aryl halide esterification, and a coupling reaction with PyBOP using the natural compound 3,4,5-trimethoxybenzoic acid as a starting material. The products were structurally characterized using 1H and 13C nuclear magnetic resonance, infrared spectroscopy, and high-resolution mass spectrometry for the unpublished compounds. The compound 4-methoxy-benzyl 3,4,5-trimethoxybenzoate (9) presented an IC50 of 46.21 µM, high selectively (SI > 16), and caused apoptosis in SCC9 cancer cells. The molecular modeling study suggested a multi-target mechanism of action for the antitumor activity of compound 9 with CRM1 as the main target receptor.

A Narrative Review of the Antitumor Activity of Monoterpenes from Essential Oils: An Update.

Monoterpenes are a group of natural products that have been widely studied due to their therapeutic potential against various pathologies. These compounds are abundant in the chemical composition of essential oils. Cancer is a term that covers more than 100 different types of malignant diseases and is among the leading causes of death in the world. Therefore, the search for new pharmacotherapeutic options applicable to cancer is urgent. In this review, studies on the antitumor activity of monoterpenes found in essential oils were selected, and botanical, chemical, and pharmacological aspects were discussed. The most investigated monoterpenes were carvacrol and linalool with highly significant in vitro and in vivo tumor inhibition in several types of cancers. The action mechanisms of these natural products are also presented and are wildly varied being apoptosis the most prevalent followed by cell cycle impairment, ROS production, autophagy, necroptosis, and others. The studies reported here confirm the antitumor properties of monoterpenes and their anticancer potential against various types of tumors, as demonstrated in in vitro and in vivo studies using various types of cancer cells and tumors in animal models. The data described serve as a reference for the advancement in the mechanistic studies of these compounds and in the preparation of synthetic derivatives or analogues with a better antitumor profile.