Naturally, thiophenes represent a small family of natural metabolites featured by one to five thiophene rings. Numerous plant species belonging to the family Asteraceae commonly produce thiophenes. These metabolites possessed remarkable bioactivities, including antimicrobial, antiviral, anti-inflammatory, larvicidal, antioxidant, insecticidal, cytotoxic, and nematicidal properties. The current review provides an update over the past seven years for the reported natural thiophene derivatives, including their sources, biosynthesis, spectral data, and bioactivities since the last review published in 2015. Additionally, with the help of the SuperPred webserver, an AI (artificial intelligence) tool, the potential drug target for the compounds was predicted. In silico studies were conducted for Cathepsin D with thiophene derivatives, including ADMET (drug absorption/distribution/metabolism/excretion/and toxicity) properties prediction, molecular docking for the binding interaction, and molecular dynamics to evaluate the ligand–target interaction stability under simulated physiological conditions.

Pluchea indica (L.) Less. (Asteraceae) commonly known as Indian camphorweed, pluchea, or marsh fleabane has gained great importance in various traditional medicines for its nutritional and medicinal benefits. It is utilized to cure several illnesses such as lumbago, kidney stones, leucorrhea, inflammation, gangrenous and atonic ulcer, hemorrhoids, dysentery, eye diseases, itchy skin, acid stomach, dysuria, abdominal pain, scabies, fever, sore muscles, dysentery, diabetes, rheumatism, etc. The plant or its leaves in the form of tea are commonly used for treating diabetes and rheumatism. The plant is a rich source of calcium, vitamin C, dietary fiber, and β-carotene. Various biomolecules have been isolated from P. indica, including thiophenes, terpenes, quinic acids, sterols, lignans, phenolics, and flavonoids. The current review reports detailed information about the phytoconstituents and pharmacological relevance of P. indica and the link to its traditional uses. The reported studies validated the efficacy and safety of P. indica, as well as supported its traditional uses for treating various ailments and promoting health and well-being. Thus, this could encourage the development of this plant into a healthy food supplement or medicine for the prevention and treatment of various diseases. However, further studies on the drug interactions, mechanism of action, pharmacokinetics, toxicology, and metabolism, as well as clinical trials, should be carried out.

Different classes of phytochemicals were previously isolated from the Red Sea algae Hypnea musciformis as sterols, ketosteroids, fatty acids, and terpenoids. Herein, we report the isolation of three fatty acids—docosanoic acid 4, hexadecenoic acid 5, and alpha hydroxy octadecanoic acid 6—as well as three ceramides—A (1), B (2), and C (3)—with 9-methyl-sphinga-4,8-dienes and phytosphingosine bases. Additionally, different phytochemicals were determined using the liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (LC-ESI-HRMS) technique. Ceramides A (1) and B (2) exhibited promising in vitro cytotoxic activity against the human breast adenocarcinoma (MCF-7) cell line when compared with doxorubicin as a positive control. Further in vivo study and biochemical estimation in a mouse model of Ehrlich ascites carcinoma (EAC) revealed that both ceramides A (1) and B (2) at doses of 1 and 2 mg/kg, respectively, significantly decreased the tumor size in mice inoculated with EAC cells. The higher dose (2 mg/kg) of ceramide B (2) particularly expressed the most pronounced decrease in serum levels of vascular endothelial growth factor -B (VEGF-B) and tumor necrosis factor-α (TNF-α) markers, as well as the expression levels of the growth factor midkine in tumor tissue relative to the EAC control group. The highest expression of apoptotic factors, p53, Bax, and caspase 3 was observed in the same group that received 2 mg/kg of ceramide B (2). Molecular docking simulations suggested that ceramides A (1) and B (2) could bind in the deep grove between the H2 helix and the Ser240-P250 loop of p53, preventing its interaction with MDM2 and leading to its accumulation. In conclusion, this study reports the cytotoxic, apoptotic, and antiangiogenic effects of ceramides isolated from the Red Sea algae Hypnea musciformis in an experimental model of EAC.

Lung cancer is a dangerous type of cancer in men and the third leading cause of cancer-related death in women, behind breast and colorectal cancers. Thymoquinone (THQ), a main compound in black seed essential oils, has a variety of beneficial effects, including antiproliferative, anti-inflammatory, and antioxidant properties. On the other hand, scorpion venom peptides (SV) induce apoptosis in the cancer cells, making it a promising anticancer agent. THQ, SV, and Phospholipon^® 90H (PL) were incorporated in a nano-based delivery platform to assess THQ’s cellular uptake and antiproliferative efficacy against a lung cancer cell line derived from human alveolar epithelial cells (A549). Several nanovesicles were prepared and optimized using factorial experimental design. The optimized phytosome formulation contained 79.0 mg of PL and 170.0 mg of SV, with vesicle size and zeta potential of 209.9 nm and 21.1 mV, respectively. The IC50 values revealed that A549 cells were significantly more sensitive to the THQ formula than the plain formula and THQ. Cell cycle analysis revealed that THQ formula treatment resulted in significant cell cycle arrest at the S phase, increasing cell population in this phase by 22.1%. Furthermore, the THQ formula greatly increased cell apoptosis (25.17%) when compared to the untreated control (1.76%), plain formula (11.96%), or THQ alone (13.18%). The results also indicated that treatment with THQ formula significantly increased caspase-3, Bax, Bcl-2, and p53 mRNA expression compared to plain formula and THQ. In terms of the inflammatory markers, THQ formula significantly reduced the activity of TNF-α and NF-κB in comparison with the plain formula and THQ only. Overall, the findings from the study proved that a phytosome formulation of THQ could be a promising therapeutic approach for the treatment of lung adenocarcinoma.

Drought is among the most common abiotic stresses that significantly influence plants’ growth and metabolic activities. In this study, Eriocephalus africanus L. (Asteraceae) was exposed to three levels of drought stress (irrigation with 75, 50, and 25% field capacity), together with foliar spraying of a plant hormone, salicylic acid (1, 2, and 3 mM SA), to observe the effect of drought stress and SA on its secondary metabolites. These growing conditions efficiently affected its total flavonoid and polyphenol contents (TFC and TPC, respectively). TFC and TPC increased by 53% and 35%, respectively, in stressed plants. Consequently, the radical scavenging activity improved by 140%. UPLC-ESI-MS/MS profiles of the extracts of control and stressed plants were assessed. Among identified polyphenols, 3,4-dicaffeoylquinic acid predominated in both samples, although it was detected in a greater percentage of stressed plants. Essential oils hydro-distilled from the plants showed a higher yield (1.05 ± 0.03% v/w) in stressed plants. Artemisia ketone prevailed in all oil samples’ GC/MS chromatograms, with a higher yield (42%) recorded in stressed plants. In conclusion, drought stress and SA spraying triggered the production of phenolic and essential oil components and increased the radical scavenging activity of E. africanus. Thus, agricultural conditions are optimized to provide a continuous supply of plant materials with appropriate amounts of bioactive constituents for economic industrialization.