Current Topics in Medicinal Chemistry - Volume 21, Issue 26, 2021

Background: Larrea tridentata is a dominant shrub in the deserts of North America and is recognized for its various traditional uses. More than 50 traditional uses have been recorded. Regarding its chemical composition, the products of the mevalonate, shikimate, and malonate pathways are predominant. L. tridentata has nordihydroguaiaretic acid (NDGA), one of its most studied secondary metabolites that exhibited remarkable different biological activities: sequestration of reactive oxygen species, inhibition of lipoxygenases (LOX) and activation of the endogenous antioxidant response mediated by nuclear factor erythroid 2-related factor 2 (NRF2). Objective and Methods: This review seeks to draw attention to metabolites other than NDGA and which also contribute to the various biological activities of L. tridentata. Therefore, the present review includes those reports focused on the pharmacological properties of the organic extracts of L. tridentata and its natural products with promising values. Results and Conclusion: Among the most promising and widely reported metabolites from L. tridentata, are: 3’-demethoxy-6-O-demethylisoguaiacin, 3’-O-methyldihydroguaiaretic acid, meso-dihydroguaiaretic acid, and tetra-O-methylnordihydroguaiaretic acid. These have been reported to exhibit antibacterial, antiprotozoal, anthelmintic, antifungal, antiviral, anticancer, and antioxidant activities.

Natural products are an important source of bioactive molecules. However, the development of biological applications based on these compounds is hindered by intrinsic problems in their solubility, volatility, degradation, and bioavailability. Nanocarriers as drug administration systems promise to overcome these limitations by providing controlled and directed delivery. This review aims to present 1) the most frequently used nanocarriers as natural product administration systems, based on the progress of controlled and directed release, and 2) the challenges associated with the use of nanocarriers as therapeutic agents.

The natural product specialized metabolites produced by microbes and plants are the backbone of our current drugs. Ironically, we are in a golden age of understanding natural product biosynthesis, biochemistry, and engineering. These advances have the potential to usher in a new era of natural product exploration and development, taking full advantage of the unique and favorable properties of natural product compounds in drug discovery. There is now an increasing realization that these privileged structures represent the optimal starting point for the development of clinically viable assets. Here, we outline the current state-of-the-art in antimicrobial natural product drug discovery, specifically Streptomyces species, with a specific focus on how the emerging field of synthetic biology is delivering the tools and technologies required to unlock the therapeutic potential of natural products. We illustrate how these approaches are circumventing many of the problems that have historically plagued conventional screening programs, enabling the expedient discovery of new molecules with novel functions.

Lichens are a symbiotic association between a fungus (mycobiont) and a green algae/- cyanobacterium (photobiont). Lichens are a source of secondary metabolites, most of them being exclusively for these species, among which dibenzofurans are found. Dibenzofurans are a small group (over 35 different identified compounds), being usnic acid the most studied. In the last 10 years, there has been a growing interest in the pharmacological activity of dibenzofurans. In this work, dibenzofurans isolated from lichens (alectosarmentin, condidymic acid, didymic acid, isousnic acid, isostrepsilic acid, usimines A-C and usnic acid) were reviewed, most of which showed antibacterial, antifungal, and cytotoxic activities. These findings provide future guidance for research on pharmacological activity of dibenzofurans.

Background: Cissus incisa is a Vitaceae with a pantropical distribution. In northern Mexico, its leaves have traditionally been used to treat skin infections, abscesses and tumors. Despite its medicinal uses, few studies have been reported. Objective: The objective of this study is to summarize the phytochemical and biological studies carried out so far on the leaves of C. incisa, since this part of the plant is the one frequently used, and awaken scientific interest towards the plant. Methods: Since C. incisa was an undocumented species, most of the information comes from reports of our research group. Databases, books, and websites were also consulted. The information collected was organized and presented in a synthesized way. Plant name was checked with the database “The Plant List”. Results: 171, 260, and 114 metabolites were identified by UHPLC-QFTOF-MS in the hexane, chloroform/ methanol, and aqueous extracts, respectively. Fatty acyls, sphingolipids, sterols, glycerolipids, prenol lipids, and terpenes are common metabolites found in these extracts. 2-(2´-hydroxydecanoyl amino)-1,3,4-hexadecanotriol-8-ene, 2,3-dihydroxypropyl tetracosanoate, β-sitosterol, β-sitosterol-D-glucopyranoside, α-amyrin-3-O-β-D-glucopyranoside were also isolated and characterized. Extracts, phytocompounds and semi-synthetic derivatives showed antimicrobial activity against multi-drug resistant bacteria and various cancer cell lines. Results from Perturbation- Theory-Machine Learning-Information-Fusion model (PTMLIF), molecular docking, and vesicular contents assay identified potential targets on the cell membrane, suggesting an antibacterial mechanism of action for ceramides from C. incisa leaves. Conclusion: This review reports the efforts of the scientific community in authenticating species used in traditional medicine. Moreover, it gives a compendium of phytochemistry and the biological activities of the components from C. incisa leaves.

Background and Objective: Osteoporosis is a worldwide healthcare challenge. Conventional medications for osteoporosis prevention are not clinically effective or associated with gastrointestinal tract adverse effects. The present study aimed to comparatively investigate the effects of technetium-99 conjugated with methylene diphosphonate (⁹⁹Tc-MDP) and calcium carbonate and alendronate on the prevention and treatment of osteoporosis in glucocorticoid-induced osteoporosis rabbit model through evaluating bone alkaline phosphatase (B-ALP), TRAP-5b levels and histopathological parameters. Methods: Forty healthy female New Zealand rabbits were randomly divided into five groups (each n=8), including control group (Control Group), osteoporosis model group (GIO Group), osteoporosis model + ⁹⁹Tc-MDP group (⁹⁹Tc-MDP Group), osteoporosis model + alendronate group (Alendronate Group), and osteoporosis model + calcium carbonate group (calcium carbonate Group). Animals in each group were treated with corresponding interventions for 14 weeks. The blood samples were collected at the first and 14th week, and B-ALP and TRAP-5b levels were detected by enzyme- linked immunosorbent assay (ELISA). The rabbits were anesthetized at the 14th week, and pathological cytological observation was performed on both femurs. Results: The age and weights of rabbits in different groups had no statistically significant differences (P>0.05). B-ALP levels in serum of all groups except for the Control Group decreased after treatment, but the differences were not statistically significant (P>0.05). TRAP-5b levels in serum of all groups increased after treatment. Specifically, differences in the GIO Group and calcium carbonate group were statistically significant (P<0.05), while differences in ⁹⁹Tc-MDP Group and alendronate Group were not statistically significant (P<0.05). Pathological sections revealed that the control group presented normal bone tissue morphology. The bone tissue morphology of the ⁹⁹Tc- MDP group and alendronate group was similar to control group and GIO group. Moreover, the calcium carbonate group and GIO group exhibited similar bone tissue morphology. Conclusion: ⁹⁹Tc-MDP has a preventive effect on the glucocorticoid-induced osteoporotic rabbit model. This osteoporosis preventive effect might be attributed to the capacities of ⁹⁹Tc-MDP in promoting the osteoblasts generation and inhibiting the generation and reducing the activity of osteoclasts.