- Indazole hydrazide compound and application thereof
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The invention provides an indazole hydrazide compound as shown in a formula (I), wherein R is selected from substituted alkyl, substituted alkenyl or substituted phenyl; substituent groups in the substituted alkyl group and the substituted alkenyl group comprise phenyl and/or substituted phenyl; and R' is selected from H or alkyl. Compared with the prior art, the indole hydrazide compound provided by the invention can be used as an integrin avbeta3 receptor antagonist, has obvious anti-prostatic cancer activity, and has a significant inhibition effect on enzalutamide drug-resistant cell lines.
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Paragraph 0089; 0091; 0095-0101; 0110-0113
(2021/06/13)
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- Suprafenacine, an Indazole-hydrazide agent, target Cancer cells through microtubule destabilization
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Microtubules are a highly validated target in cancer therapy. However, the clinical development of tubulin binding agents (TBA) has been hampered by toxicity and chemoresistance issues and has necessitated the search for new TBAs. Here, we report the identification of a novel cell permeable, tubulin-destabilizing molecule - 4,5,6,7-tetrahydro-1H-indazole-3- carboxylic acid [1p-tolyl-meth-(E)-ylidene]-hydrazide (termed as Suprafenacine, SRF). SRF, identified by in silico screening of annotated chemical libraries, was shown to bind microtubules at the colchicine-binding site and inhibit polymerization. This led to G2/M cell cycle arrest and cell death via a mitochondria-mediated apoptotic pathway. Cell death was preceded by loss of mitochondrial membrane potential, JNK - mediated phosphorylation of Bcl-2 and Bad, and activation of caspase-3.Intriguingly, SRF was found to selectively inhibit cancer cell proliferation and was effective against drug-resistant cancer cells by virtue of its ability to bypass the multidrug resistance transporter P-glycoprotein. Taken together, our resultssuggest that SRF has potential as a chemotherapeutic agent for cancer treatment and provides an alternate scaffold for the development of improved anti-cancer agents.
- Choi, Bo-Hwa,Chattopadhaya, Souvik,Thanh, Le Nguyen,Feng, Lin,Nguyen, Quoc Toan,Lim, Chuan Bian,Harikishore, Amaravadhi,Reddy, Ravi Prakash,Bharatham, Nagakumar,Zhao, Yan,Liu, Xuewei,Yoon, Ho Sup
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- TUBULIN INHIBITORS
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The present invention relates to a compound of Formula (I) for use as a medicament, wherein: m is 0, 1, 2, 3, 4, or 5; R1 and R2 together form a five-membered, six-membered, or seven-membered ring, wherein R1 and R2 together as a group is -(CH2)3-, -(CH2)4 -, or -(CH2)5-; R3 at each occurrence is independently selected from the group consisting of H, halogen, hydroxyl, alkoxy, and a substituted or unsubstituted C1-C5 alkyl; and R4 is H, halogen, or a substituted or unsubstituted C1-C5 alkyl
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Paragraph 00225
(2013/11/18)
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