Development of 1,2,3-triazole hybrids as multi-faced anticancer agents co-targeting EGFR/mTOR pathway and tubulin depolymerization.

Novel 1,2,3-triazole hybrids bearing various substituents have been synthesized as potential anticancer agents. Ligand-based approach has been adopted to design these compounds relying on the hybridization of 1,2,3-triazole with α,β-unsaturated carbonyl, 5- and 6-membered heterocyclic scaffolds. All synthesized members were investigated for their cytotoxic potency against nine types comprising 60 panels of human cancerous cells by the US National Cancer Institute: Development Therapeutic Program (US_NCI_DTP).

Design, synthesis and biological evaluation of new series of hexahydroquinoline and fused quinoline derivatives as potent inhibitors of wild-type EGFR and mutant EGFR (L858R and T790M).

New series of hexahydroquinoline and fused quinoline derivatives were designed and synthesized. The thirty seven new compounds were screened for in vitro antitumor activity against HepG2, HCT-116 and MCF-7 cancer cells. Results indicated that compounds 2e, 2h, 5b, 5c, 6a, 7d and 9b have the strongest potency against the three cancer cells, and they were further screened for in vitro cytotoxicity against A431 and H1975 cancer cells, as well as WI38 and WISH normal cells.

1,4,5,6,7,8-Hexahydroquinolines and 5,6,7,8-tetrahydronaphthalenes: A new class of antitumor agents targeting the colchicine binding site of tubulin.

New series of 2-amino-1,4,5,6,7,8-hexahydroquinoline-3-carbonitriles 3a,b and 2-amino-5,6,7,8-tetrahydronaphthalene-1,3-dicarbonitriles 4a-h were synthesized and evaluated for their antitumor activity. In vitro antitumor screening of the new members against HepG2, HCT-116 and MCF-7 cancer cells showed that the tetrahydronaphthalene-1,3-dicarbonitrile 4c has the highest potency against the three tested cancer cells (IC = 6.02, 8.

Synthesis of α-indolylacrylates as potential anticancer agents using a Brønsted acid ionic liquid catalyst and the butyl acetate solvent.

In this study, new α-indolylacrylate derivatives were synthesized by the reaction of 2-substituted indoles with various pyruvates using a Brønsted acid ionic liquid catalyst in butyl acetate solvent. This is the first report on the application of pyruvate compounds for the synthesis of indolylacrylates. The acrylate derivatives could be obtained in good to excellent yields.

Pooled library screening with multiplexed Cpf1 library.

Capitalizing on the inherent multiplexing capability of AsCpf1, we developed a multiplexed, high-throughput screening strategy that minimizes library size without sacrificing gene targeting efficiency. We demonstrated that AsCpf1 can be used for functional genomics screenings and that an AsCpf1-based multiplexed library performs similarly as compared to currently available monocistronic CRISPR/Cas9 libraries, with only one vector required for each gene. We construct the smallest whole-genome CRISPR knock-out library, Mini-human, for the human genome (n = 17,032 constructs targeting 16,977 protein-coding genes), which performs favorably compared to conventional Cas9 libraries.