Tryptophan derived natural marine alkaloids and synthetic derivatives as promising antimicrobial agents.

Antimicrobial resistance has become a major threat to public health worldwide, as pathogenic microorganisms are finding ways to evade all known antimicrobials. Therefore, the demand for new and effective antimicrobial agents is also increasing. Natural products have always played an important role in drug discovery, either by themselves or as inspiration for synthetic compounds. The marine environment is a rich source of bioactive metabolites, and among them, tryptophan-derived alkaloids stand out for their abundance and by displaying a variety of biological activities, with antimicrobial properties being among the most significant. This review aims to reveal the potential of marine alkaloids derived from tryptophan as antimicrobial agents. Relevant examples of these compounds and their synthetic analogues reported in the last decades are presented and discussed in detail, with their mechanism of action and synthetic approaches whenever relevant. Several tryptophan-derived marine alkaloids have shown potent and promising antimicrobial activities, whether against bacteria, fungi, or virus. Synthetic approaches to many of the compounds have been developed and recent methodologies are proving to be efficient. Even though most of the studies regarding the antimicrobial activity are still preliminary, this class of compounds has proven to be worth of further investigation and may provide useful lead compounds for the development of antimicrobial agents. Overall, marine alkaloids derived from tryptophan are revealed as a valuable class of antimicrobials and molecular modifications in order to reduce the toxicity of these compounds and additional studies regarding their mechanism of action are interesting topics to explore in the future.

Efficacy, Stability, and Safety Evaluation of New Polyphenolic Xanthones Towards Identification of Bioactive Compounds to Fight Skin Photoaging.

Antioxidants have long been used in the cosmetic industry to prevent skin photoaging, which is mediated by oxidative stress, making the search for new antioxidant compounds highly desirable in this field. Naturally occurring xanthones are polyphenolic compounds that can be found in microorganisms, fungi, lichens, and some higher plants. This class of polyphenols has a privileged scaffold that grants them several biological activities. We have previously identified simple oxygenated xanthones as promising antioxidants and disclosed as hit, 1,2-dihydroxyxanthone (1). Herein, we synthesized and studied the potential of xanthones with different polyoxygenated patterns as skin antiphotoaging ingredients. In the DPPH antioxidant assay, two newly synthesized derivatives showed IC50 values in the same range as ascorbic acid. The synthesized xanthones were discovered to be excellent tyrosinase inhibitors and weak to moderate collagenase and elastase inhibitors but no activity was revealed against hyaluronidase. Their metal-chelating effect (FeCl3 and CuCl2) as well as their stability at different pH values were characterized to understand their potential to be used as future cosmetic active agents. Among the synthesized polyoxygenated xanthones, 1,2-dihydroxyxanthone (1) was reinforced as the most promising, exhibiting a dual ability to protect the skin against UV damage by combining antioxidant/metal-chelating properties with UV-filter capacity and revealed to be more stable in the pH range that is close to the pH of the skin. Lastly, the phototoxicity of 1,2-dihydroxyxanthone (1) was evaluated in a human keratinocyte cell line and no phototoxicity was observed in the concentration range tested.

Lichen Xanthones as Models for New Antifungal Agents.

Due to the emergence of multidrug-resistant pathogenic microorganisms, the search for new antimicrobial compounds plays an important role in current medicinal chemistry research. Inspired by lichen antimicrobial xanthones, a series of novel chlorinated xanthones was prepared using five chlorination methods (Methods A⁻E) to obtain different patterns of substitution in the xanthone scaffold. All the synthesized compounds were evaluated for their antimicrobial activity. Among them, 3-chloro-4,6-dimethoxy-1-methyl-9H-xanthen-9-one 15 showed promising antibacterial activity against E. faecalis (ATCC 29212 and 29213) and S. aureus ATCC 29213. 2,7-Dichloro-3,4,6-trimethoxy-1-methyl-9H-xanthen-9-one 18 revealed a potent fungistatic and fungicidal activity against dermatophytes clinical strains (T. rubrum, M. canis, and E. floccosum (MIC = 4⁻8 µg/mL)). Moreover, when evaluated for its synergistic effect for T. rubrum, compound 18 exhibited synergy with fluconazole (ΣFIC = 0.289). These results disclosed new hit xanthones for both antibacterial and antifungal activity.

Anticancer and cancer preventive compounds from edible marine organisms.

A direct impact of food on health, which demonstrates that dietary habit is one of the most important determinants of chronic diseases such as cancers, has led to an increased interest of the consumers toward natural bioactive compounds as functional ingredients or nutraceuticals. Epidemiological studies revealed that the populations of many Asian countries with high consumption of fish and seafood have low prevalence of particular type of cancers such as lung, breast, colorectal and prostate cancers. This observation has led to extensive investigations of the benefits of compounds present in edible marine organisms such as fish, marine invertebrates (mollusks, echinoderms) and marine algae as cancer chemopreventive agents. Interestingly, many of these marine organisms not only constitute as seafood delicacy but also as ingredients used in folk medicine of some East and Southeast Asian countries. The results of the investigations on extracts and compounds from fish (cods, anchovy, eel and also fish protein hydrolysates), mollusks (mussel, oyster, clams and abalone), as well as from sea cucumbers on the in vivo/in vitro anticancer/antitumor activities can, in part, support the health benefits of these edible marine organisms.

Effect of abietane diterpenes from Plectranthus grandidentatus on the growth of human cancer cell lines.

Five known abietane diterpenes, fatty acid esters of 7alpha-acyloxy-6beta-hydroxyroyleanone (1), grandidone A (2), 7alpha-acetoxy-6beta-hydroxyroyleanone (3), 6beta,7alpha-dihydroxyroyleanone (4), and coleon U (5), isolated from Plectranthus grandidentatus Gürke, were evaluated for their in vitro antiproliferative activity against five human cancer cell lines MCF-7, NCI-H460, SF-268, TK-10, and UACC-62. Coleon U (5) exhibited the strongest effect among all the assayed compounds. The abietane 3 revealed also a strong inhibitory effect while diterpenes 2 and 4 inhibited only slightly the growth of all cancer cell lines.