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Medicinal plants indicated for chronic diseases usually have good safety margins as they are intended for lifelong treatments. We hypothesized that they may provide patients with baseline protection to cancers and multidrug resistance-reversing phytochemicals resulting in successful prevention and/or adjuvant treatment of chemotherapy-resistant cancers. We selected 27 popular herbal infusions widely used in Nigeria for diabetes and studied their effects on a panel of liver (HepG2), colon (Caco2), and skin (B16-F10) cancer cells. Cytotoxicity was measured using the SRB staining assay. The 2D antimigratory effect was evaluated using an Oris™ platform. The P-glycoprotein (P-gp) efflux activity was evaluated using Rh-123 as a fluorescent probe. The inhibition of tyrosinase-mediated melanogenesis was evaluated by colorimetric enzymatic assays. Our results show that melanoma cell proliferation was strongly inhibited by (Combretaceae) (Phyllanthaceae), (Leguminosae), and (Myrtaceae) extracts (G 50 µg/ml). (Apocynaceae), (Asclepiadaceae), and (Apocynaceae) were preferentially toxic against Caco2 (GI 50, 5 and 35 µg/ml, respectively). The most active extracts against different drug resistance mechanisms were (inhibition of P-gp efflux, and impairing tyrosinase activity) and (inhibition of P-gp efflux). (Meliaceae), , and (Combretaceae) significantly inhibited B16-F10 cell migration. Lupeol, ursolic acid, quercitrin, epicatechin, gallic acid, and ellagic acid were dereplicated by HPLC and HPTLC as their bioactive phytochemicals. In conclusion, the above in-vitro activities of herbal infusions regularly consumed by Nigerian diabetic patients may either act as a baseline chemoprotection or as sensitizing agents.
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http://dx.doi.org/10.3389/fphar.2020.546439 | DOI Listing |
J Med Chem
September 2025
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States.
Proteasome inhibitors are effective in treating hematologic cancers but have limited utility in brain tumors due to poor blood-brain barrier (BBB) penetration and metabolic instability. In this study, we developed novel macrocyclic peptide epoxyketone inhibitors with improved drug-like properties. Compounds were screened for cytotoxicity against brain cancer cell lines, permeability (PAMPA-BBB and Caco-2), and metabolic stability.
View Article and Find Full Text PDFMol Pharm
September 2025
Division of Pharmaceutics and Pharmacology, College of Pharmacy; Center for RNA Nanotechnology and Nanomedicine; James Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, Ohio 43210, United States.
Liver cancer, particularly hepatocellular carcinoma (HCC), poses significant treatment challenges due to chemoresistance and cancer recurrence. Similar to customs at the border, the liver detoxifies incoming chemicals via efflux pumps and overexpresses ATP-binding cassette (ABC) drug exporters, leading to chemoresistance. ABC contains a multihomosubunit structure and a revolving transport mechanism, actively effluxing drugs from cancer cells, thereby reducing intracellular drug accumulation and therapeutic efficacy.
View Article and Find Full Text PDFRSC Med Chem
August 2025
College of Pharmaceutical Science & Green Pharmaceutical Collaborative Innovation Center of Yangtze River Delta Region, Zhejiang University of Technology Hangzhou 310014 China
The overexpression of P-glycoprotein (P-gp) has been recognized as a pivotal factor contributing to the emergence of multidrug resistance (MDR), a phenomenon that frequently limits the efficacy of chemotherapy and profoundly impacts patient prognosis. Consequently, the inhibition of P-gp's efflux function has become a critical therapeutic strategy for overcoming drug resistance and enhancing chemotherapeutic efficacy. In recent years, the development of P-gp inhibitors has garnered significant attention, particularly with the frequent incorporation of heterocyclic derivatives, which exhibit exceptional biological activity and favorable chemical properties, into drug design.
View Article and Find Full Text PDFBioorg Chem
September 2025
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, People's Republic of China. Electronic address:
Chemical investigation of the twigs and leaves of Euphorbia tirucalli afforded six undescribed tigliane glycosides, tirucalosides A-F (1-6), together with 12 known diterpenoids (7-18). Compound 1 represents a rare carbon skeleton bearing a 5/7/5/4-fused ring system, while compound 6 contains an unusual seco-glucoside substitution. Their structures were determined by a combination of an extensive spectroscopic analysis and acid hydrolysis experiment.
View Article and Find Full Text PDFBackground Fentanyl is a potent synthetic opioid widely used for pain management and anesthesia, but the high prevalence of its misuse and its key contribution to overdose fatalities in the United States have made it a major drug of concern. Although fentanyl's onset, duration, and toxicity depend on its pharmacokinetics and specific tissue distribution, most studies have focused primarily on plasma concentrations, leaving its distribution in critical tissues largely unexplored (this knowledge gap limits our understanding of fentanyl's clinical effects, tissue accumulation, and the factors influencing its efficacy and safety). Here, we report the radiosynthesis of [ C]fentanyl for PET imaging and present a preliminary whole-body pharmacokinetic study in rodents.
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