92579-89-0Relevant academic research and scientific papers
Synthesis of thiazole linked indolyl-3-glyoxylamide derivatives as tubulin polymerization inhibitors
Guggilapu, Sravanthi Devi,Guntuku, Lalita,Reddy, T. Srinivasa,Nagarsenkar, Atulya,Sigalapalli, Dilep Kumar,Naidu,Bhargava, Suresh K.,Bathini, Nagendra Babu
, p. 83 - 95 (2017/06/27)
A series of thiazole linked indolyl-3-glyoxylamide derivatives were synthesized and evaluated for their in vitro cytotoxic activity against DU145 (prostate), PC-3 (prostate), A549 (lung) and HCT-15 (colon) cancer cell lines by employing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among all the synthesized compounds, compound 13d displayed cytotoxicity of IC50 = 93 nM towards DU145 cancer cell line. The most active compound 13d was also tested on RWPE-1 cells and was found to be safe compared to the DU145 cells. The target compounds were also evaluated for their inhibition activity of tubulin polymerization. Further, the treatment of compound 13d on DU145 cells led to the inhibition of cell migration ability. The detailed studies such as acridine orange/ethidium Bromide (AO/EB), DAPI, annexin V-FITC/propidium iodide staining assay suggested that the compound 13d induced apoptosis in DU145 cells. The influence of the cytotoxic compound 13d on the cell cycle distribution was assessed on the DU145 cell line, exhibiting a cell cycle arrest at the G2/M phase. Moreover, the treatment with compound 13d caused collapse of mitochondrial membrane potential and elevated intracellular ROS levels in DU145 cells. The results from molecular modelling studies revealed that these compounds bind at the colchicine binding site of the tubulin. Thus, this new molecular scaffold could be a new lead for the development of anticancer agents that target tubulin.
Synthesis and biological activity of novel mono-indole and mono-benzofuran inhibitors of bacterial transcription initiation complex formation
Mielczarek, Marcin,Thomas, Ruth V.,Ma, Cong,Kandemir, Hakan,Yang, Xiao,Bhadbhade, Mohan,Black, David Stc.,Griffith, Renate,Lewis, Peter J.,Kumar, Naresh
, p. 1763 - 1775 (2015/03/30)
Our ongoing research focused on targeting transcription initiation in bacteria has resulted in synthesis of several classes of mono-indole and mono-benzofuran inhibitors that targeted the essential protein-protein interaction between RNA polymerase core and σ70/σA factors in bacteria. In this study, the reaction of indole-2-, indole-3-, indole-7- and benzofuran-2-glyoxyloyl chlorides with amines and hydrazines afforded a variety of glyoxyloylamides and glyoxyloylhydrazides. Similarly, condensation of 2- and 7-trichloroacetylindoles with amines and hydrazines delivered amides and hydrazides. The novel molecules were found to inhibit the RNA polymerase-σ70/σA interaction as measured by ELISA, and also inhibited the growth of both Gram-positive and Gram-negative bacteria in culture. Structure-activity relationship (SAR) studies of the mono-indole and mono-benzofuran inhibitors suggested that the hydrophilic-hydrophobic balance is an important determinant of biological activity.
Sulfur rich 2-mercaptobenzothiazole and 1,2,3-triazole conjugates as novel antitubercular agents
Mir, Fauzia,Shafi, Syed,Zaman,Kalia, Nitin Pal,Rajput, Vikrant S.,Mulakayala, Chaitanya,Mulakayala, Naveen,Khan, Inshad A.,Alam
, p. 274 - 283 (2014/03/21)
A series of benzfused heterocyclic derivatives such as amide conjugates of 2-(benzo[d]thiazol-2-ylthio)acetic acid with aromatic/aliphatic/cyclic secondary amines (5a-5o & 8a-8m); 1,2,3-triazole conjugates of 2- mercaptobenzothiazoles and amide conjugates of indole-3-glyoxalic acid with cyclic secondary amines (14a-14g) have been synthesized and were screened for their antitubercular activity against Mycobacterium tuberculosis H37Rv strain by broth microdilution assay method. Compounds 8b, 8f, 8g and 8l inhibited the growth of the H37Rv strain at concentrations of 8 μg/mL. These compounds (8b, 8f, 8g and 8l) have been further identified as bactericidal and are completely killing the microbes at 32-64 μg/mL concentrations. Molecular docking studies of the active compounds reveal that these compounds are targeting DprE1 and may act as DprE1 inhibitors.
Synthesis and evaluation of indole-based new scaffolds for antimicrobial activities - Identification of promising candidates
Singh, Palwinder,Verma, Puja,Yadav, Bhawna,Komath, Sneha S.
, p. 3367 - 3372 (2011/06/24)
Search for new antimicrobial agents led to the synthesis of series of N-1, C-3 and C-5 substituted bis-indoles. Their evaluation for antifungal and antibacterial activities resulted in the optimization of pyrrolidine/morpholine/ N-benzyl moiety at the C-3 end and propane/butane/xylidine groups as linkers between two indoles for significant inhibition of microbial growth. Preliminary investigations have identified three highly potent antimicrobial agents. Dockings of these molecules in the active sites of lanosterol demethylase, dihydrofolate reductase and topoisomerase II indicate their strong interactions with these enzymes.
