RESUMO
Given the widespread and established use of Jasminum scandens (Retz) Vahl, a member of the Oleacea family, this study aimed to identify and characterise secondary metabolites derived from the plant, with the objective of evaluating their potential biological activities. Using chromatographic separations techniques based on molecular weight and polarity, various VLC fractions of the plant were purified. These fractions yielded seven compounds- 2-(4-hydroxyphenyl)-ethanol (1), 2-(4-hydroxy-3-methoxy-phenyl)-ethanol (2), 1-(4-hydroxy-3-methoxy-phenyl)-1,2,3-propanetriol (3), 1-(4-hydroxy-3,5-dimethoxy-phenyl)-1,2,3-propanetriol (4), lupeol (5), ß-sitosterol (6), and methyl linoleate (7), which have never been previously reported in this plant. Out of the seven identified compounds, compounds 3 and 4 had the greatest capacity to scavenge free radicals with IC50 values of 3.81 µg/ml and 4.08 µg/ml, respectively when compared to the standard Butylated Hydroxy Toluene (BHT) with IC50 value of 6.54 µg/ml.
RESUMO
Anticancer drug conjugates may benefit from simultaneous action at two targets potentially overcoming the drawbacks of current cancer treatment, such as insufficient efficacy, high toxicity, and development of resistance. Compared to a combination of two single-target drugs, they may offer an advantage of pharmacokinetic simplicity and fewer drug-drug interactions. Here, we report a series of compounds connecting tamoxifen or endoxifen with the EGFR-inhibitor gefitinib via a covalent linkage. These hybrid ligands retain both ER antagonist activity and EGFR inhibition. The most potent analogues exhibited single-digit nanomolar activities at both targets. The amide-linked endoxifen-gefitinib drug conjugates 17b and 17c demonstrated the most favorable anti-cancer profile in cellular viability assays on MCF7, MDA-MB-231, MDA-MB-468, and BT-549 breast cancer cells. Most importantly, in TNBC cells 17b and 17c displayed nanomolar IC50-values (380 nM - 970 nM) and were superior in their anti-cancer activity compared to their control compounds and combinations thereof.
