869304-06-3Relevant academic research and scientific papers
Design, synthesis and anticancer evaluation of tetrahydro-β-carboline-hydantoin hybrids
Shankaraiah, Nagula,Nekkanti, Shalini,Chudasama, Karmarajsinh J.,Senwar, Kishna Ram,Sharma, Pankaj,Jeengar, Manish Kumar,Naidu,Srinivasulu, Vunnam,Srinivasulu, Gannoju,Kamal, Ahmed
, p. 5413 - 5417 (2014)
A series of new tetrahydro-β-carboline-hydantoin hybrids have been designed and synthesized based on the structure of the known Eg5 inhibitor HR22C16. These compounds have been evaluated for their anticancer activity against lung (A549), cervical (ME180, HeLa), prostate (PC-3) and breast (MCF-7) cancer cell lines by MTT assay. These hybrids have displayed significant in vitro cytotoxicity in comparison to etoposide against PC-3, A549, and MCF-7 cell lines. The hybrids 3a, 3b, 3c, 3e, 3f, 3g, 4b, 4c, 4e and 4f appear to be more effective against the PC-3 cell line, among which compound 4b displayed the highest cytotoxicity (6.08 ± 0.2, IC50 μM). Based on these results, an attempt was made to rationalize their mechanism of action through cell cycle analysis studies. The flow-cytometric analysis of compound 4b in PC-3 cells indicated a G2/M cell cycle arrest. Molecular docking studies substantiate that these compounds indeed bind to the allosteric site of Eg5 formed from Glu116, Gly117, Glu118, Trp127, Ala133, Ile136, Pro137, Tyr211, Leu214, and Glu215 residues with the most potent compound 4b showing the most favorable interaction.
Synthesis and biological evaluation of functionalised tetrahydro-β- carboline analogues as inhibitors of Toxoplasma gondii invasion
Walton, Jeffrey G. A.,Patterson, Stephen,Liu, Gu,Haraldsen, Jeralyn D.,Hollick, Jonathan J.,Slawin, Alexandra M. Z.,Ward, Gary E.,Westwood, Nicholas J.
supporting information; experimental part, p. 3049 - 3060 (2011/02/25)
Techniques for the identification of the protein target(s) of small molecules are proving very important following an increase in the use of phenotype-based screening in chemical biology and drug discovery. One approach, known as the yeast-3-hybrid approach, has shown considerable potential. A key factor in the success of this approach is the preparation of a complex molecule referred to as a chemical inducer of dimerisation (CID). The synthesis of two CIDs based on a bioactive tetrahydro-β-carboline core structure is reported and evidence presented that shows the CIDs are of utility in this approach. A series of chemo- and bioinformatic studies coupled with SAR development inspired the choice of CIDs.
Synthesis and biological evaluation of new tetrahydro-β-carbolines as inhibitors of the mitotic kinesin Eg5
Sunder-Plassmann, Nils,Sarli, Vasiliki,Gartner, Michael,Utz, Mathias,Seiler, Jeanette,Huemmer, Stefan,Mayer, Thomas U.,Surrey, Thomas,Giannis, Athanassios
, p. 6094 - 6111 (2007/10/03)
The mitotic kinesin Eg5 (or KSP) is a crucial player in the development and function of the mitotic spindle. Inhibition of this protein leads to cell cycle arrest and apoptosis without interfering with other microtubule-dependent processes. Therefore, it
