Furthermore, molecular docking studies revealed that complex 1 was successfully localized inside the binding pocket of protein kinase (Akt), which validate the mechanism and mode of interaction of 1 that displayed cytotoxic activity experimentally. The obtained outcomes reveal that the complex 1 could be utilized as an encouraging perspective in the development of new therapeutic candidate for colon cancer.In this research, betulin derivatives were bonded to the 1,4-quinone fragment by triazole linker. Furthermore, the enzymatic assay used has shown that these compounds are a good DT-diaphorase (NQO1) substrates as evidenced by increasing enzymatic conversion rates relative to that of streptonigrin. The anticancer activities of the hybrids were tested against a panel of human cell lines, like melanoma, ovarian, breast, colon, and lung cancers. The structure-activity relationship showed that the activity depends on the type of 1,4-quinone moiety and the tumor cell lines used. It was also found that the anticancer effects were increasing against the cell line with higher NQO1 protein level, like breast (T47D, MCF-7), colon (Caco-2), and lung (A549) cancers. The transcriptional activity of the gene encoding a proliferation marker (H3 histone), cell cycle regulators (p53 and p21) and apoptosis pathway (BCL-2 and BAX) for selected compounds were determined. The molecular docking study was carried out to examine the interaction between the hybrids and NQO1 enzyme. The computational simulation showed that the type of the 1,4-quinone moiety influences location of the compound in the active site of the enzyme. It is worth noting that the study of new hybrids of betulin as substrate for NQO1 protein may lead to new medical therapeutic applications in the future.Seven new diterpenoids (1-7), including five 7-membered ring vibsane-type diterpenoids, vibsanolide A-E (1-5) and a pair of epimers of 14,15,16,17-tetranorvibsane-type diterpenoids possessing bicyclo[4.2.1]nonane moiety, vibsanolide F-G (6-7), together with twelve known analogues (8-19) were isolated from the crude extracts of the leaves of Viburnum odoratissimum using Small Molecule Accurate Recognition Technology (SMART). These structures including absolute configurations were elucidated by means of comprehensive analyses of spectroscopic data, as well as comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. These compounds were evaluated for their cytotoxic activities against A549 and HepG2 cells by MTT assay. The results showed that compound 2 exhibited potent cytotoxic activity against A549 cells with IC50 value of 1.11 μM. Further staining experiments indicated that 2 could promote apoptosis induction, enhance reactive oxygen species (ROS) level and attenuate mitochondrial membrane potential (MMP) in A549 cells. Taken together, these findings provided new insights into understanding the cytotoxic activity of vibsane-type diterpenoids and it is meaningful to further investigate the application potential of V. odoratissimum.Bruton’s tyrosine kinase (BTK) is a member of the Tec kinase family and plays a key role in the modulation of the B-cell receptor (BCR)-mediated signaling pathway. PLK inhibitor Inhibition of BTK has been proven to be an effective therapeutic approach for various hematological malignancies, such as chronic lymphocytic leukemia (CLL), mantle cell leukemia (MCL), diffuse large B-cell lymphoma (DLBCL) and acute myeloid leukemia (AML). Here, a new series of imidazole group-substituted arylaminopyrimidines (IAAPs) were designed and synthesized as potent inhibitors of the enzymatic activity of BTK with a half maximal inhibitory concentration (IC50) ranging from 13.10 to 42.40 nM. In particular, 11a and 11b exhibited stronger antiproliferative activity against AML and B lymphomas cell lines compared with BTK inhibitor ibrutinib and showed low cytotoxicity against normal peripheral blood mononuclear cells (PBMCs). In addition, analysis of the mechanism of action of these compounds revealed that 11a and 11b induced significant apoptosis in AML and B lymphoma cells by arresting the cell cycle at the G1/G0 or G2/M stage and blocked BTK autophosphorylation as well as the ensuing abrogation of pro-survival AKT and ERK signaling. Taken together, these results suggest that 11a and 11b might serve as valuable preclinical candidates for the treatment of AML and B-cell lymphoma.Nineteen indole alkaloids including eleven new ones, taberdines A-K (1-11), were isolated from Tabernaemontana divaricata. Their structures were assigned by MS, NMR, single crystal X-ray diffractions, and ECD analyses. Alkaloid 1 is an aspidosperma-type monoterpenoid indole alkaloid and possesses a rearranged pyrrolidine moiety due to C-3 degradation, and 4 has a rare 1,3-oxazolidine moiety within iboga-type alkaloids. Alkaloids 2, 4, 6, and 11-19 combined with 5 μg/mL fluconazole exhibited significant activity to reverse fluconazole resistance in Candida albicans strains while no one used alone showed any activities against the resistant strain.In this study, a novel series of 4,6,7-trisubstituted quinoline analogues bearing thiazolidinones were designed and synthesized based on our previous study. Among them, the most potent compound 15i, 4-((4-(4-(3-(2-(2,6-difluorophenyl)-4-oxothiazolidin-3-yl)ureido)-2-fluorophenoxy)-6-methoxyquinolin-7-yl)oxy)-N,N-diethylpiperidine-1-carboxamide was identified as a multi-kinase inhibitor. The results of MTT assay revealed in vitro antitumor activities against HT-29 cells of compound 15i with an IC50 value of 0.19 μM which was 14.5-fold more potent than that of Regorafenib. In the cellular context, significant antiproliferation, cytotoxicity and induction of apoptosis on HT-29 cells in a dose- and time-dependent manner were confirmed by IncuCyte live-cell imaging assays. Moreover, compound 15i strongly induced apoptosis by arresting cell cycle into the G2/M phase. No antiproliferation and cytotoxicity against human normal colorectal mucosa epithelial cell FHC was observed at 10.0 μg/mL or lower concentrations which indicated that the toxicity to normal cells of compound 15i was much lower than that of Regorafenib. Based on the above findings, further structural modification will be conducted for the development of more potent kinase inhibitors as anticancer agents.