The Impact of Geographical Location on the Chemical Compositions of Pimpinella lutea Desf. Growing in Tunisia

Essential oils are generally produced to confer the protection of medicinal plants against several natural enemies. Variations of chemical and physical environmental factors exert significant influences on plant development. They hence may affect the quality and quantity of volatile organic metabolites of interest and, therefore, the economic applications of essential oils. This research focused on the effects of the harvest region on the production and analytes present in Tunisian Pimpinella lutea Desf. Apiaceae that were collected in three different growing environments (North and South Bizerta and Tabarka). Essential oils extracted from a variety of genotypes were analyzed, for the first time, using gas chromatography and mass spectrometry (GC/FID and GC/MS). The determination of the percentage of essential oil components allowed the recognition of three chemotypes: α-trans-Bergamotene quantified at a percentage of 18.1% in North Bizerta (NBEO), muurola-4,10(14)-dien-1-β-ol identified in South Bizerta (10.1%, SBEO) and acora-3,7(14)-dien present in a high level of 29.1% in Tabarka population (TEO). The richness of different populations in sesquiterpenes (60.2–78.1%) suggests that Pimpinella lutea Desf. may be used in different industrial segments

EAPB0503, a novel imidazoquinoxaline derivative, inhibits growth and induces apoptosis in chronic myeloid leukemia cells

International audienceImatinib, the first-generation tyrosine kinase inhibitor, revolutionized the therapeutic management of chronic myeloid leukemia (CML) and is highly effective in inducing remissions and prolonging the survival of CML patients. However, one-third of patients develop intolerance or resistance to treatment, and CML stem cells remain insensitive to this therapy, leading almost inevitably to relapse upon treatment discontinuation. Imidazoquinoxalines are imiquimod derivatives that induce growth inhibition and induction of caspase-dependent apoptosis in melanoma and T-cell lymphoma cells. We investigated the effects of EAPB0203 and EAPB0503, two novel imidazoquinoxaline derivatives, on human CML cell lines and showed that they induced a dose-dependent and time-dependent cell growth inhibition. EAPB0503 proved more potent and induced a specific cell cycle arrest in mitosis in CML cells and direct activation of apoptosis as evidenced by increased pre-G0 population, breakdown of mitochondrial membrane potential, PARP cleavage, and DNA breakage. Interestingly, EAPB0503 decreased BCR-ABL oncoprotein levels. The combination of EAPB0503 with imatinib synergized to inhibit the proliferation of CML cells, and most importantly, EABP0503 inhibited the proliferation of imatinib-resistant CML cells, offering promising therapeutic modalities that would circumvent resistance to tyrosine kinase inhibitors and improve the prognosis of CML