Bengamide Analogues Show A Potent Antitumor Activity against Colon Cancer Cells: A Preliminary Study

Abstract

The limited success and side effects of the current chemotherapeutic strategies against colorectal cancer (CRC), the third most common cancer worldwide, demand an assay with new drugs. The prominent antitumor activities displayed by the bengamides (Ben), a family of natural products isolated from marine sponges of the Jaspidae family, were explored and investigated as a new option to improve CRC treatment. To this end, two potent bengamide analogues, Ben I (5) and Ben V (10), were selected for this study, for which they were synthesized according to a new synthetic strategy recently developed in our laboratories. Their antitumor effects were analyzed in human and mouse colon cell lines, using cell cycle analysis and antiproliferative assays. In addition, the toxicity of the selected analogues was tested in human blood cells. These biological studies revealed that Ben I and V produced a significant decrease in CRC cell proliferation and induced a significant cell cycle alteration with a greater antiproliferative effect on tumor cell lines than normal cells. Interestingly, no toxicity effects were detected in blood cells for both compounds. All these biological results render the bengamide analogues Ben I and Ben V as promising antitumoral agents for the treatment of CRC.

The Development of the Bengamides as New Antibiotics against Drug-Resistant Bacteria

“…Mar. Drugs 2022, 20, x FOR PEER REVIEW 8 of 22 potent analogues described so far, analogue 28, against colorectal cancer (CRC) cell lines as a new alternative treatment of colon cancer [35]. A preliminary antitumor evaluation against different tumor and non-tumor cell lines revealed this analogue as a very potent antitumor compound in the low micromolar range, although not so potent as previously described by Nan et al (Table 3).…”

“…These stunning biological discoveries elicited the emerging interest for the bengamides as new potential antibiotics, and as a result, some bengamide analogues have been developed and proved to possess impressive antibiotic activities against various drug-resistant bacteria such as Mycobacterium tuberculosis and Staphylococcus aureus, expanding the biological applications of these enticing molecules. The interest of our research group in the design and development of new antitumor agents based on bioactive natural products, led us to consider the bengamides as prime targets, starting a research programme directed to the establishment of an efficient, stereoselective and convergent synthesis that enabled the access to the natural bengamides [30][31][32] and analogs thereof for biological evaluations [33][34][35].…”

“…The present review reports all these new discoveries, describing in detail the evolution of the bengamides from their initial exploration as antitumor agents up to their current status as antibiotics, highlighting the manifold value of these marine natural products as valid hits in medicinal chemistry. The interest of our research group in the design and development of new antitumor agents based on bioactive natural products, led us to consider the bengamides as prime targets, starting a research programme directed to the establishment of an efficient, stereoselective and convergent synthesis that enabled the access to the natural bengamides [30][31][32] and analogs thereof for biological evaluations [33][34][35].…”

“…Based on the excellent and striking antitumor properties of some of the described analogues, in our research group, we decided to evaluate the viability of one of their most Based on the excellent and striking antitumor properties of some of the described analogues, in our research group, we decided to evaluate the viability of one of their most potent analogues described so far, analogue 28, against colorectal cancer (CRC) cell lines as a new alternative treatment of colon cancer [35]. A preliminary antitumor evaluation against different tumor and non-tumor cell lines revealed this analogue as a very potent antitumor compound in the low micromolar range, although not so potent as previously described by Nan et al (Table 3).…”

Aaptamine-rich Fraction from the Indonesian Marine Sponge, Aaptos suberitoides, Exhibits a Cytotoxic Effect on DLD-1 Colorectal Cancer Cells

“…Colon cancer, known as colorectal adenocarcinoma (CRC), is a type of cancer with the third most frequent cases in both men and women worldwide [1] and ranks the fourth cause of death [2]. CRC arises from glands in the epithelial cells of the large intestine followed by a series of mutations, replication, and increasing survival.…”