319429-81-7

Upstream product

• 140-87-4 Cyanoacetohydrazide 
• 6630-33-7 ortho-bromobenzaldehyde 

Downstream Products

• 1136642-15-3 1,6‐diamino‐4‐(2‐bromophenyl)‐2‐oxo‐1,2‐dihydropyridine‐3,5‐dicarbonitrile 

Relevant academic research and scientific papers

Design, synthesis, anticancer, and docking of some S- and/or N-heterocyclic derivatives as VEGFR-2 inhibitors

Novel heterocyclic derivatives (4–22) were designed, synthesized, and evaluated against hepatocellular carcinoma type (HepG2) and breast cancer (MCF-7) cells, targeting the VEGFR-2 enzyme. Compounds 18, 10, 13, 11, and 14 were found to be the most potent derivatives against both the HepG2 and MCF-7 cancer cell lines, with GI50 = 2.11, 2.54 μM, 3.16, 3.64 μM, 3.24, 6.99 μM, 7.41, 6.49 μM and 8.08, 10.46 μM, respectively. Compounds 18 and 10 showed higher activities against both HepG2 and MCF-7 cells than sorafenib (GI50 = 9.18, 5.47 μM, respectively) and doxorubicin (GI50 = 7.94, 8.07 μM, respectively). Compounds 13, 11, and 14 showed higher activities than sorafenib against HepG2 cancer cells, but lower activities against MCF-7 cells. Compounds 18, 13, and 10 were more potent than sorafenib, inhibiting vascular endothelial growth factor receptor-2 (VEGFR-2) at GI50 values of 0.05, 0.06, and 0.08 μM, respectively. Compound 11 inhibited VEGFR-2 at an IC50 value of 0.10 μM, which is equipotent to sorafenib. Compound 14 inhibited VEGFR-2 at an IC50 value of 0.11 μM, which is nearly equipotent to sorafenib. The tested compounds have more selectivity against cancer cell lines. Compounds 18, 10, 13, 11, and 14 are, respectively, 16.76, 9.24, 6.06, 2.78, and 2.85 times more toxic in HePpG2 cancer cells than in VERO normal cells. Also, compounds 18, 10, 13, 11, and 14 are, respectively, 14.07, 8.02, 2.81, 3.18, and 2.20 times more toxic in MCF-7 than in VERO normal cells. The most active compounds, 10, 13, and 18, showed a good ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile.

Pyridine-derived VEGFR-2 inhibitors: Rational design, synthesis, anticancer evaluations, in silico ADMET profile, and molecular docking

Novel pyridine-derived compounds (5–19) were designed and?synthesized, and their anticancer activities were evaluated against HepG2 and MCF-7 cells, targeting the VEGFR-2 enzyme. Compounds 10, 9, 8, and 15 were found to be the most potent derivatives against the two cancer cell lines,?HepG2 and MCF-7, respectively, with IC50 = 4.25 and 6.08 μM, 4.68 and 11.06 μM, 4.34 and 10.29 μM, and 6.37 and 12.83 μM. Compound 10 displayed higher activity against HepG2 cells than sorafenib (IC50 = 9.18 and 5.47 μM, respectively) and doxorubicin (IC50 = 7.94 and 8.07 μM, respectively). It also showed higher activity than doxorubicin against MCF-7 cells, but lower activity than sorafenib. Compounds 9, 8, and 15 displayed higher activities than sorafenib and doxorubicin against HepG2 cells but exhibited lower activities against MCF-7 cells. Compound 10 potently inhibited VEGFR-2 at an IC50 value of 0.12 μM, which is nearly equipotent to sorafenib (IC50 = 0.10 μM). Compounds 8 and 9 exhibited very good activity with the same IC50 value of 0.13 μM. The six most potent derivatives, 6, 9, 8, 10, 15, and 18, were tested for their cytotoxicity against normal Vero cells. Compounds 6, 8, 9, 10, 15, and 18 are, respectively, 1.13, 3.74, 4.18, 3.64, 2.81, and 2.00 times more toxic to HepG2 and 2.06, 1.58, 1.76, 2.54, 1.40, and 2.69 times more toxic to MCF-7 breast cancer cells than in normal Vero cells.

Mechanistic differences between in vitro assays for hydrazone-based small molecule inhibitors of anthrax lethal factor

A systematically generated series of hydrazones were analyzed as potential inhibitors of anthrax lethal factor. The hydrazones were screened using one UV-based and two fluorescence-based in vitro assays. The study identified several inhibitors with IC50 values in the micromolar range, and importantly, significant differences in the types of inhibition were observed with the different assays.