Showing papers by "Wannian Zhang published in 2015"
TL;DR: Antitumor mechanism and target profiling studies indicate that compound 66c is the first-in-class triple topoisomerase I/topoisomersase II/tubulin inhibitor.
Abstract: A critical question in natural product-based drug discovery is how to translate the product into drug-like molecules with optimal pharmacological properties. The generation of natural product-inspired scaffold diversity is an effective but challenging strategy to investigate the broader chemical space and identify promising drug leads. Extending our efforts to the natural product evodiamine, a diverse library containing 11 evodiamine-inspired novel scaffolds and their derivatives were designed and synthesized. Most of them showed good to excellent antitumor activity against various human cancer cell lines. In particular, 3-chloro-10-hydroxyl thio-evodiamine (66c) showed excellent in vitro and in vivo antitumor efficacy with good tolerability and low toxicity. Antitumor mechanism and target profiling studies indicate that compound 66c is the first-in-class triple topoisomerase I/topoisomerase II/tubulin inhibitor. Overall, this study provided an effective strategy for natural product-based drug discovery.
142 citations
TL;DR: The successful cases from the recent five year studies are used to illustrate how these approaches are implemented to uncover and optimize small molecule PPI inhibitors and notably some of them have become promising therapeutics.
Abstract: Correction for 'State-of-the-art strategies for targeting protein-protein interactions by small-molecule inhibitors' by Chunquan Sheng et al., Chem. Soc. Rev., 2015, DOI: 10.1039/c5cs00252d.
126 citations
TL;DR: A powerful divergent cascade strategy has been explored for the easy construction of diverse enantioenriched pyrazole-derived scaffolds from readily available chiral fused pyrazoles-tetrahydropyran acetals, revealing potent anticancer lead compounds that deserve further development.
58 citations
TL;DR: A series of hybrid molecules designed and synthesized on the basis of 3-amino-10-hydroxylevodiamine and SAHA proved to be a potent inhibitor of topoisomerase I/II and HDAC with good antiproliferative and apoptotic activities.
Abstract: Designing multitarget drugs remains a significant challenge in current antitumor drug discovery. Because of the synergistic effect between topoisomerase and HDAC inhibitors, the present study reported the first-in-class triple inhibitors of topoisomerase I/II and HDAC. On the basis of 3-amino-10-hydroxylevodiamine and SAHA, a series of hybrid molecules was successfully designed and synthesized. In particular, compound 8c was proven to be a potent inhibitor of topoisomerase I/II and HDAC with good antiproliferative and apoptotic activities. This proof-of-concept study also validated the effectiveness of discovering triple topoisomerase I/II and HDAC inhibitors as novel antitumor agents.
57 citations
TL;DR: The first example of the successful simplification of an antifungal natural product is provided, starting from sampangine, and two novel simplified scaffolds with excellent antIFungal activity were discovered.
34 citations
TL;DR: In this paper, isomers of evodiamine derivatives 2 and 3 were obtained by straightforward asymmetric total synthesis and their inhibitory activities toward topoisomerases I and II and their cytotoxicities in cancer cell lines were evaluated.
11 citations
TL;DR: A series of novel triazole antifungal agents containing piperidine-oxadiazole side chains were rationally designed and synthesized and showed excellent inhibitory activity against clinically important fungal pathogens.
Abstract: Due to increasing incidence and mortality of invasive fungal infections, discovery and development of new generations of antifungal agents represents a challenging task. On the basis of our previously reported triazole-benzyloxypiperidinyl lead compound, a series of novel triazole antifungal agents containing piperidine-oxadiazole side chains were rationally designed and synthesized. Most of the target compounds showed excellent inhibitory activity against clinically important fungal pathogens. In particular, compounds 6g (MIC = 0.031 μg mL−1) and 11b (MIC = 0.016 μg mL−1) were highly active against Candida albicans including fluconazole-resistant strains. Moreover, they showed inhibitory activity against hyphal formation with low toxicity, which were promising leads for further development.
10 citations