In vitro cytotoxic effect of stigmasterol derivatives against breast cancer cells.

BACKGROUND: Stigmasterol is an unsaturated phytosterol that belong to the class of tetracyclic steroids abundant in Rhoicissus tridentata. Stigmasterol is an important constituent since it has shown impressive pharmacological effects such as anti-osteoarthritis, anticancer, anti-diabetic, anti-inflammatory, antiparasitic, immunomodulatory, antifungal, antioxidant, antibacterial, and neuroprotective activities. Furthermore, due to the presence of π system and hydroxyl group, stigmasterol is readily derivatized through substitution and addition reactions, allowing for the synthesis of a wide variety of stigmasterol derivatives. METHODS: Stigmasterol (1) isolated from Rhoicissus tridentata was used as starting material to yield eight bio-active derivatives (2-9) through acetylation, epoxidation, epoxide ring opening, oxidation, and dihydroxylation reactions. The structures of all the compounds were established using spectroscopic techniques, NMR, IR, MS, and melting points. The synthesized stigmasterol derivatives were screened for cytotoxicity against the hormone receptor-positive breast cancer (MCF-7), triple-negative breast cancer (HCC70), and non-tumorigenic mammary epithelial (MCF-12 A) cell lines using the resazurin assay. RESULTS: Eight stigmasterol derivatives were successfully synthesized namely; Stigmasterol acetate (2), Stigmasta-5,22-dien-3,7-dione (3), 5,6-Epoxystigmast-22-en-3ß-ol (4), 5,6-Epoxystigmasta-3ß,22,23-triol (5), Stigmastane-3ß,5,6,22,23-pentol (6), Stigmasta-5-en-3,7-dion-22,23-diol (7), Stigmasta-3,7-dion-5,6,22,23-ol (8) and Stigmast-5-ene-3ß,22,23-triol (9). This is the first report of Stigmasta-5-en-3,7-dion-22,23-diol (7) and Stigmasta-3,7-dion-5,6,22,23-ol (8). The synthesized stigmasterol analogues showed improved cytotoxic activity overall compared to the stigmasterol (1), which was not toxic to the three cell lines tested (EC50 ˃ 250 µM). In particular, 5,6-Epoxystigmast-22-en-3ß-ol (4) and stigmast-5-ene-3ß,22,23-triol (9) displayed improved cytotoxicity and selectivity against MCF-7 breast cancer cells (EC50 values of 21.92 and 22.94 µM, respectively), while stigmastane-3ß,5,6,22,23-pentol (6) showed improved cytotoxic activity against the HCC70 cell line (EC50: 16.82 µM). CONCLUSION: Natural products from Rhoicissus tridentata and their derivatives exhibit a wide range of pharmacological activities, including anticancer activity. The results obtained from this study indicate that molecular modification of stigmasterol functional groups can generate structural analogues with improved anticancer activity. Stigmasterol derivatives have potential as candidates for novel anticancer drugs.

Phytochemistry, Pharmacology, and Nutraceutical Profile of Carissa Species: An Updated Review.

Carissa, a genus of the Apocynaceae family, consists of evergreen species, such as shrubs as well as small trees that are native to Asia, Africa, and Oceania's subtropical and tropical regions. Most of the Carissa species are traditionally used to treat various diseases, such as chest pain, headaches, gonorrhoea, rheumatism, syphilis, oedema, rabies, stomach pain, hepatitis, cardiac diseases, and asthma. The pharmacological studies on Carissa species revealed its antioxidant, antimicrobial, anticancer, cardioprotective, antipyretic, analgesic, wound healing, anticonvulsant, antiarthritic, adaptogenic, anti-inflammatory, and antidiabetic activities, thus validating its use in indigenous medicine systems. The review article summarised the comprehensive literature available, including morphology, indigenous uses, bioactive composition, nutraceutical, and pharmacological activities of Carissa species. A total of 155 research papers were cited in this review article. The Carissa fruits are rich in dietary fibre, lipids, proteins, carbohydrates, vitamin C, and macro- and micro-elements. A total of 121 compounds (35 polyphenols (flavonoids and phenolic acids), 30 lignans, 41 terpenoids, 7 steroids, 2 coumarins, and 6 cardiac glycosides) have been extracted from C. spinarum, C. carandas, and C. macrocarpa. Among all chemical constituents, lupeol, carissol, naringin, carisssone, scopoletin, carissaeduloside A, D, J, carandinol, sarhamnoloside, carissanol, olivil, carinol, 3ß-hydroxyolean-11-en-28,13ß-oilde, ursolic acid, and carissone are the key bioactive constituents responsible for pharmacological activities of genus Carissa. The gathered ethnopharmacological information in the review will help to understand the therapeutic relevance of Carissa as well as paving a way for further exploration in the discovery of novel plant-based drugs.

Nanoparticles Functionalised with Re(I) Tricarbonyl Complexes for Cancer Theranostics.

Globally, cancer is the second (to cardiovascular diseases) leading cause of death. Regardless of various efforts (i.e., finance, research, and workforce) to advance novel cancer theranostics (diagnosis and therapy), there have been few successful attempts towards ongoing clinical treatment options as a result of the complications posed by cancerous tumors. In recent years, the application of magnetic nanomedicine as theranostic devices has garnered enormous attention in cancer treatment research. Magnetic nanoparticles (MNPs) are capable of tuning the magnetic field in their environment, which positively impacts theranostic applications in nanomedicine significantly. MNPs are utilized as contrasting agents for cancer diagnosis, molecular imaging, hyperfusion region visualization, and T cell-based radiotherapy because of their interesting features of small size, high reactive surface area, target ability to cells, and functionalization capability. Radiolabelling of NPs is a powerful diagnostic approach in nuclear medicine imaging and therapy. The use of luminescent radioactive rhenium(I), 188/186Re, tricarbonyl complexes functionalised with magnetite Fe3O4 NPs in nanomedicine has improved the diagnosis and therapy of cancer tumors. This is because the combination of Re(I) with MNPs can improve low distribution and cell penetration into deeper tissues.