70070-24-5Relevant articles and documents
Identification of new 3-phenyl-1H-indole-2-carbohydrazide derivatives and their structure–activity relationships as potent tubulin inhibitors and anticancer agents: A combined in silico, in vitro and synthetic study
Saruengkhanphasit, Rungroj,Butkinaree, Chutikarn,Ornnork, Narittira,Lirdprapamongkol, Kriengsak,Niwetmarin, Worawat,Svasti, Jisnuson,Ruchirawat, Somsak,Eurtivong, Chatchakorn
, (2021)
Virtual screening of commercially available molecular entities by using CDRUG, structure-based virtual screening, and similarity identified eight new derivatives of 3-phenyl-1H-indole-2-carbohydrazide with anti-proliferative activities. The molecules were tested experimentally for inhibition of tubulin polymerisation, which revealed furan-3-ylmethylene-3-phenyl-1H-indole-2-carbohydrazide (27a) as the most potent candidate. Molecule 27a was able to induce G2/M phase arrest in A549 cell line, similar to other tubulin inhibitors. Synthetic modifications of 27a were focussed on small substitutions on the furan ring, halogenation at R1 position and alteration of furyl connectivity. Derivatives 27b, 27d and 27i exhibited the strongest tubulin inhibition activities and were comparable to 27a. Bromine substitution at R1 position showed most prominent anticancer activities; derivatives 27b-27d displayed the strongest activities against HuCCA-1 cell line and were more potent than doxorubicin and the parent molecule 27a with IC50 values 50 = 0.34 μM), while 27d displayed stronger activity against A549 cell line (IC50 = 0.43 μM) compared to doxorubicin and 27a. Fluorine substitutions at the R1 position tended to show more modest anti-tubulin and anticancer activities, and change of 2-furyl to 3-furyl was tolerable. The new derivatives, thiophenyl 26, displayed the strongest activity against A549 cell line (IC50 = 0.19 μM), while 1-phenylethylidene 21b and 21c exhibited more modest anticancer activities with unclear mechanisms of action; 26 and 21c demonstrated G2/M phase arrest, but showed weak tubulin inhibitory properties. Molecular docking suggests the series inhibit tubulin at the colchicine site, in agreement with the experimental findings. The calculated molecular descriptors indicated that the molecules obey Lipinski's rule which suggests the molecules are drug-like structures.
Synthesis of Substituted 1,2,3,8-Tetrahydroindolobenzodiazepin-2-ones and 5,6,7,8-Tetrahydroindolobenzodiazepin-6-ones
Hiremath, Shivayogi P.,Badami, Prema S.,Purohit, Muralidhar G.
, p. 1115 - 1119 (2007/10/02)
Nitrosation (NaNO2/AcOH) of 2-phenylindoles (1a-d) and subsequent reduction of the resultant 3-nitroso-2-phenylindoles (2a-d) with sodium dithionite in alkali furnish the corresponding 3-aminoindoles (3a-d), which on condensation with ethyl chloroformate
