- Discovery of certain benzyl/phenethyl thiazolidinone-indole hybrids as potential anti-proliferative agents: Synthesis, molecular modeling and tubulin polymerization inhibition study
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A series of certain benzyl/phenethyl thiazolidinone-indole hybrids were synthesized for the study of anti-proliferative activity against A549, NCI-H460 (lung cancer), MDA-MB-231 (breast cancer), HCT-29 and HCT-15 (colon cancer) cell lines by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). We found that compound G37 displayed highest cytotoxicity with IC50 value of 0.92 ± 0.12 μM towards HCT-15 cancer cell line among all the synthesized compounds. Moreover, compound G37 was also tested on normal human lung epithelial cells (L132) and was found to be safe in contrast to HCT-15 cells. The lead compound G37 showed significant G2/M phase arrest in HCT-15 cells. Additionally, compound G37 significantly inhibited tubulin polymerization with IC50 value of 2.92 ± 0.23 μM. Mechanistic studies such as acridine orange/ethidium bromide (AO/EB) dual staining, DAPI nuclear staining, annexinV/propidium iodide dual staining, clonogenic growth inhibition assays inferred that compound G37 induced apoptotic cell death in HCT-15 cells. Moreover, loss of mitochondrial membrane potential with elevated intracellular ROS levels was observed by compound G37. These compounds bind at the active pocket of the α/β-tubulin with higher number of stable hydrogen bonds, hydrophobic and arene-cation interactions confirmed by molecular modeling studies.
- Sigalapalli, Dilep Kumar,Pooladanda, Venkatesh,Singh, Priti,Kadagathur, Manasa,Guggilapu, Sravanthi Devi,Uppu, Jaya Lakshmi,Tangellamudi, Neelima D.,Gangireddy, Pavan Kumar,Godugu, Chandraiah,Bathini, Nagendra Babu
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supporting information
(2019/08/26)
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- Thiazolidinedione derivatives, method for preparing the derivatives and pharmaceutical compositions containing same
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A thiazolidinedione derivative represented by the following general formula (I): STR1 ?wherein the dotted line represents a single bond or a double bond, the thiazolidinedione ring residue is linked to either of 2-, 3-, 4-, 5- and 6-positions on the indole ring and R represents a group selected from the group consisting of hydrogen atom and alkyl, alkenyl, alkynyl, phenyl, aralkyl, heterocycloalkyl, arylsulfonyl and arylaminocarbonyl groups! or a pharmaceutically acceptable salt thereof exhibits excellent effects of reducing the blood sugar level and of reducing the lipid concentration in blood and is accordingly useful as a therapeutic agent for treating diabates mellitus. These derivatives and pharmaceutically acceptable salt thereof are almost free of any side effect.
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- Heck Annulation on 2-Position of Indoles or 1H-Pyrrolopyridine
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1-Substituted 3-formylindoles lead to annulated indoloisoquinoline or pyrrolophenanthridine via palladium coupling.Under the same conditions 1-substituted 7-azaindoles afforded the 7-aza analogues.
- Desarbre, Eric,Merour, Jean-Yves
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p. 1987 - 1998
(2007/10/02)
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