98711-39-8Relevant academic research and scientific papers
Identification and validation of selective deubiquitinase inhibitors
Auld, Douglas,Buhrlage, Sara J.,Casalena, Dominick,Chan, Wai Cheung,Dhe-Paganon, Sirano,Hu, Bin,Liu, Xiaoxi,Magin, Robert S.,Marto, Jarrod A.,Roberts, Rebekka M.,Seo, Hyuk-Soo,Varca, Anthony C.,Zhu, He
, p. 1758 - 13,1771 (2021/12/20)
Deubiquitinating enzymes (DUBs) are a class of isopeptidases that regulate ubiquitin dynamics through catalytic cleavage of ubiquitin from protein substrates and ubiquitin precursors. Despite growing interest in DUB biological function and potential as therapeutic targets, few selective small-molecule inhibitors and no approved drugs currently exist. To identify chemical scaffolds targeting specific DUBs and establish a broader framework for future inhibitor development across the gene family, we performed high-throughput screening of a chemically diverse small-molecule library against eight different DUBs, spanning three well-characterized DUB families. Promising hit compounds were validated in a series of counter-screens and orthogonal assays, as well as further assessed for selectivity across expanded panels of DUBs. Through these efforts, we have identified multiple highly selective DUB inhibitors and developed a roadmap for rapidly identifying and validating selective inhibitors of related enzymes.
Chalcone based azacarboline analogues as novel antitubulin agents: Design, synthesis, biological evaluation and molecular modelling studies
Sharma, Sahil,Kaur, Charanjit,Budhiraja, Abhishek,Nepali, Kunal,Gupta, Manish K.,Saxena,Bedi
, p. 648 - 660 (2014/09/17)
The present study involves the design of a series of 3-aryl-9-acetyl- pyridazino[3,4-b]indoles as constrained chalcone analogues. A retrosynthetic route was proposed for the synthesis of target compounds. All the synthesized compounds were evaluated for in-vitro cytotoxicity against THP-1, COLO-205, HCT-116 and A-549 human cancer cell lines. The results indicated that 2a, 3a, 5a and 6a possessed significant cytotoxic potential with an IC50 value ranging from 1.13 to 5.76 μM. Structure activity relationship revealed that the nature of both Ring A and Ring B influences the activity. Substitution of methoxy groups on the phenyl ring (Ring A) and unsubstituted phenyl ring (Ring B) were found to be the preferred structural features. The most potent compound 2a was further tested for tubulin inhibition. Compound 2a was found to significantly inhibit the tubulin polymerization (IC50 value - 2.41 μM against THP-1). Compound 2a also caused disruption of microtubule assembly as evidenced by Immunoflourescence technique. The significant cytotoxicity and tubulin inhibition by 2a was rationalized by molecular modelling studies. The most potent structure was docked at colchicine binding site (PDB ID-1SA0) and was found to be stabilized in the cavity via various hydrophobic and hydrogen bonding interactions.
Facile one pot microwave induced solvent-free synthesis and antifungal, antitubercular screening of spiro [1,5]-benzothiazepin-2,3′[3′H] indol-2[1′H]-ones
Dandia, Anshu,Sati, Meha,Arya, Kapil,Sharma, Rekha,Loupy, Andre
, p. 1137 - 1141 (2007/10/03)
Microwave activation coupled with dry media technique as a green chemistry procedure has been applied to synthesis of a series of some new title compounds. They have been obtained by the reaction of in situ synthesized 1,3-dihydro-3-[2-(phenyl/4-fluorophenyl)-2-oxoethylidene)-indol-2(1H)-one (4a, b) with substituted aminobenzenethiols (5a - d). The key intermediates 4a, b were also prepared in one step by this improved technique by reacting isatin and substituted acetophenones (2a, b). The results obtained under microwave irradiation when compared with that following conventional method demonstrate the versatility of the process. The title compounds 7a - e have also been screened for their antifungal and antitubercular activity, 7a and 7e showing maximum inhibition of growth of Alternaria alternata and Fusarium oxysporium and 7b, c, e revealing significant antitubercular activity.
Investigation on the reactions of fluorine containing 1,3-dihydro-3-(2-phenyl-2-oxoethylidene)-2H-indol-2-ones with hydrazine derivatives
Joshi, Krishna C,Dandia, Anshu,Bhagat, Sunita
, p. 98 - 104 (2007/10/02)
Reactions of fluorine containing 1,3-dihydro-3-(2-phenyl-2-oxoethylidene)-2H-indol-2-ones (II) with various hydrazines have been studied in different media.Reaction of II with hydrazine hydrate in abs. ethanol gives 2',4'-dihydro-5'-phenylspiro3H-indole-
STUDIES IN SPIROHETEROCYCLES: PART X: REACTIONS OF DIAZOMETHANE WITH 3-AROYLMETHYLENE-INDOL-2-ONES AND SYNTHESIS OF SOME NOVEL FLUORINE CONTAINING SPIRO-2'(1'H)-ONES
Joshi, Krishna C.,Jain, Renuka,Arora, Seema
, p. 1835 - 1839 (2007/10/02)
Reaction of ethereal diazomethane with fluorinated 3-aroylmethylene-indol-2-ones has been investigated for the first time yielding spiro-2'(1'H)-ones.The structures of all compounds have been confirmed on the basis of elemental
