Current Topics in Medicinal Chemistry - Volume 22, Issue 19, 2022

Ethnopharmacological Relevance: Plants of the genus Euphorbia have long been used as traditional medicine in China, Europe, America, Turkey, India, Africa, Iran, and Pakistan for their great medicinal value and health benefits. Their stems, leaves, roots, and latex are widely used to treat respiratory infections, body and skin irritations, digestive disorders, inflammatory infections, body pain, snake or scorpion bites, pregnancy, sensory disturbances, microbial and anticancer diseases. Objectives: This review aims to provide updated information on the genus Euphorbia, including traditional medicinal uses, valuation and exploitation of medicinal plants, phytochemistry, botanical characterization, pharmacological and toxicological research focused on the medicinal properties of several Euphorbias in particular their antibacterial, anti-tumor, and cell manifestations, in addition to the effect of each isolated bioactive molecule from these species and their pharmacological use including preclinical evaluation of new drugs. Materials and Methods: This work was conducted using scientific databases such as: PubMed, Google Scholar, Scopus, Science Direct, etc. In addition, ChemDraw software has been used for the drawing of chemical molecules. The correct names of the plants were confirmed from plantlist.org. The results of this review research were interpreted, analyzed and documented based on the bibliographical information obtained. Results: Among all the species of the Euphorbiaceae family, 15 species have been demonstrated to exhibit anticancer activity, 21 species have antibacterial activity, and 10 species have cytotoxic activity. The majority of the chemical constituents of this plant include triterpenoid glycosides, diterpenoids, flavonoids, and the 4α-methyl steroids. Among them, the main bioactive constituents are present in the diterpenoid fraction. The study of more than 33 steroid plants identified more than 104 compounds. Pharmacological research proved that the crude extracts and some pure compounds obtained from Euphorbia had activities for the treatment of different diseases. The objective of the present study was focused on cytotoxic, antibacterial and antitumor diseases. The study of the phytochemistry of the Euphorbia families led to the conclusion that all the plants studied had active compounds, of which 27 plants were characterized by their cytotoxic effects, 7 had antibacterial effects and 10 plants had anti-tumor activities. Therefore, the safety of Euphorbia herbal medicine should be considered a top priority in the early stages of development and clinical trials. Conclusion: Many previous studies have validated many traditional uses of Euphorbia species. The latex of some Euphorbia species seems to be toxic however, studies dealing with the safety and quality of these species are still incomplete. Extensive studies are needed on the Euphorbia plants before they can be fully used in clinics as a potent drug candidate, as researchers are focusing mainly on diterpenoids and triterpenoids, while there are many other types of compounds that may possess new biological activities.

Over the last 50 years, the number of patients with mycotic infections has gradually increased. Amphotericin-B is a gold-standard drug used in serious systemic fungal infections. However, limited solubility and permeability are challenging issues associated with Amphotericin-B. Chemical modification is one of the ways to get its broader applicability and improved physicochemical properties. The review article provides a comprehensive overview of the chemical modification approach for investigating the mechanism of action, biological activity, bioavailability, and toxicity of Amphotericin B. Further, several drug delivery approaches have also been utilized to provide better therapeutic outcomes. This gives an overview of chemical approaches for exploring various factors associated with Amphotericin B and information on its drug delivery approaches for improved biopharmaceutical outcomes.

Schistosomiasis ranks among the most important infectious diseases, with over 200 million people currently being infected and > 280,000 deaths reported annually. Chemotherapeutic treatment has relied on one drug, praziquantel, for four decades, while other drugs, such as oxamniquine and metrifonate, are no longer preferred for clinical use due to their narrow spectrum of activity - these are only active against S. mansoni and S. haematobium, respectively. Despite being cheap, safe, and effective against all schistosome species, praziquantel is ineffective against immature worms, which may lead to reinfections and treatment failure in endemic areas; a situation that necessitates repeated administration besides other limitations. Therefore, novel drugs are urgently needed to overcome this situation. In this paper, an up to date review of drug targets identified and validated against schistosomiasis while also encompassing promising clinical and preclinical candidate drugs is presented. While there are considerable efforts aimed at identifying and validating drug targets, the pipeline for new antischistosomals is dry. Moreover, the majority of compounds evaluated preclinically are not really advanced because most of them were evaluated in very small preclinical species such as mice alone. Overall, it appears that although a lot of research is going on at discovery phases, unfortunately, it does not translate to advanced preclinical and clinical evaluation.

Background: Leprosy (Hansen’s disease) is a neglected tropical disease affecting millions of people globally. The combined formulations of dapsone, rifampicin and clofazimine (multidrug therapy, MDT) is only supportive in the early stage of detection, while “reemergence” is a significant problem. Thus, there is still a need to develop newer antileprosy molecules either of natural or semi-synthetic origin. Objectives: The review intends to present the latest developments in the disease prevalence, available therapeutic interventions and the possibility of identifying new molecules from phytoextracts. Methods: Literature on the use of plant extracts and their active components to treat leprosy was searched. Selected phytoconstituents were subjected to molecular docking study on both wild and mutant types of the Mycobacterium leprae. Since the M. leprae dihydropteroate synthase (DHPS) is not available in the protein data bank (PDB), it was modelled by the homology model method and validated with the Ramachandran plot along with other bioinformatics approaches. Two mutations were introduced at codons 53 (Thr to Ile) and 55 (Pro to Leu) for docking against twenty-five selected phytoconstituents reported from eight plants that recorded effective anti-leprosy activity. The chemical structure of phytochemicals and the standard dapsone structure were retrieved from the PubChem database and prepared accordingly for docking study with the virtual-screening platform of PyRx-AutoDock 4.1. Results: Based on the docking score (kcal/mol), most of the phytochemicals exhibited a higher docking score than dapsone. Asiaticoside, an active saponin (-11.3, -11.2 and -11.2 kcal/mol), was proved to be the lead phytochemical against both wild and mutant types DHPS. Some other useful phytoconstituents include echinocystic acid (-9.6, -9.5 and -9.5 kcal/mol), neobavaisoflavone (-9.2, -9.0 and -9.0 kcal/mol), boswellic acid (-8.90, -8.90 and -8.90 kcal/mol), asiatic acid (-8.9, -8.8 and -8.9 kcal/mol), corylifol A (-8.8, 8.0, and -8.0), etc. Overall, the computational predictions support the previously reported active phytoextracts of Centella asiatica (L.) Urban, Albizia amara (Roxb.) Boivin, Boswellia serrata Roxb. and Psoralea corylifolia L. to be effective against leprosy. Conclusion: A very small percentage of well-known plants have been evaluated scientifically for antileprosy activity. Further in vivo experiments are essential to confirm anti-leprosy properties of such useful phytochemicals.

Background: The fractionation of the n-hexane phase of the EtOH extract from the leaves of Duguetia lanceolata (Annonaceae) led to the identification of the sesquiterpene (–)-cyclocolorenone. Objectives: Chemical characterization, including determination of the absolute stereochemistry, and in vitro evaluation of antileishmanial activity of the sesquiterpene (–)-cyclocolorenone, isolated from D. lanceolata, were carried out. Methods: (–)-Cyclocolorenone was isolated from D. lanceolata leaves using different chromatographic steps and its structure was defined by analysis of NMR and ESI-HRMS data. Additionally, the absolute configuration of (–)-cyclocolorenone was ambiguously assigned by means of vibrational circular dichroism (VCD). Antileishmanial activity of (–)-cyclocolorenone was evaluated on promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. The integrity of the cell membrane of L. (L.) amazonensis was analyzed using the SYTOX green probe. Results: (–)-(1R,6S,7R,10R)-Cyclocolorenone displayed activity against promastigotes and amastigotes forms of L. (L.) amazonensis with IC50 of 4.54 and 28.44 μM, respectively. Furthermore, this compound was non-toxic in J774 macrophage cells (CC50 > 458.71 μM) with a selectivity index > 100 (promastigotes) and > 32.2 (amastigotes). Additionally, (–)-cyclocolorenone was observed to target the parasite cell membrane. Conclusion: Obtained data suggested that (–)-cyclocolorenone, in which absolute configuration was determined, can be considered as a scaffold for the development of new drugs for the treatment of leishmaniasis.