1879-56-7Relevant articles and documents
Targeting HIF-1α by newly synthesized Indolephenoxyacetamide (IPA) analogs to induce anti-angiogenesis-mediated solid tumor suppression
Al-Ostoot, Fares Hezam,Sherapura, Ankith,V, Vigneshwaran,Basappa, Giridhara,H.K, Vivek,B.T, Prabhakar,Khanum, Shaukath Ara
, p. 1328 - 1343 (2021/05/03)
Background: Hypoxic microenvironment is a common feature of solid tumors, which leads to the promotion of cancer. The transcription factor, HIF-1α, expressed under hypoxic conditions stimulates tumor angiogenesis, favoring HIF-1α as a promising anticancer agent. On the other hand, synthetic Indolephenoxyacetamide derivatives are known for their pharmacological potentiality. With this background here, we have synthesized, characterized, and validated the new IPA (8a–n) analogs for anti-tumor activity. Methods: The new series of IPA (8a–n) were synthesized through a multi-step reaction sequence and characterized based on the different spectroscopic analysis FT-IR, 1H, 13C NMR, mass spectra, and elemental analyses. Cell-based screening of IPA (8a–n) was assessed by MTT assay. Anti-angiogenic efficacy of IPA (8k) validated through CAM, Rat corneal, tube formation and migration assay. The underlying molecular mechanism is validated through zymogram and IB studies. The in vivo anti-tumor activity was measured in the DLA solid tumor model. Results: Screening for anti-proliferative studies inferred, IPA (8k) is a lead molecule with an IC50 value of ?5?μM. Anti-angiogenic assays revealed the angiopreventive activity through inhibition of HIF-1α and modulation downstream regulatory genes, VEGF, MMPs, and P53. The results are confirmative in an in vivo solid tumor model. Conclusion: The IPA (8k) is a potent anti-proliferative molecule with anti-angiogenic activity and specifically targets HIF1α, thereby modulates its downstream regulatory genes both in vitro and in vivo. The study provides scope for new target-specific drug development against HIF-1α for the treatment of solid tumors. Graphic abstract: [Figure not available: see fulltext.].
The Novel 4-Phenyl-2-Phenoxyacetamide Thiazoles modulates the tumor hypoxia leading to the crackdown of neoangiogenesis and evoking the cell death
Mohammed, Yasser Hussein Eissa,Malojirao, Vikas H.,Thirusangu, Prabhu,Al-Ghorbani, Mohammed,Prabhakar,Khanum, Shaukath Ara
, p. 1826 - 1839 (2017/11/16)
Tumor microenvironment is a complex multistep event which involves several hallmarks that transform the normal cell into cancerous cell. Designing the novel antagonistic molecule to reverse the tumor microenvironment with specific target is essential in modern biological studies. The novel 4-phenyl-2-phenoxyacetamide thiazole analogues 8a-ab were synthesized in multistep process, then screened and assessed for cytotoxic and anti-proliferative effects in vitro against multiple cancer cells of different origin such as MCF-7, A549, EAC and DLA cells which revealed that compound 8f with fluoro and methyl substitute has potential cytotoxic efficacy with an average IC50 value of ? 13 μM. The mechanism of cytotoxicity assessed for anti-tumor studies both in ascites and solid tumor models in-vivo inferred the regressed tumor activity. This is due to changes in the cause of tumor microenvironment with crackdown of neovascularization and evoking apoptosis process as assessed by CAM, corneal vascularization and apoptotic hallmarks in 8f treated cells. The molecular gene studies inferred involvement of HIF-1upregulation and stabilization of p53 which are interlinked in signaling as conferred by immunoblot analysis.
Finding new elicitors that induce resistance in rice to the white-backed planthopper Sogatella furcifera
He, Xingrui,Yu, Zhaonan,Jiang, Shaojie,Zhang, Peizhi,Shang, Zhicai,Lou, Yonggen,Wu, Jun
supporting information, p. 5601 - 5603 (2015/11/17)
Herein we report a new way to identify chemical elicitors that induce resistance in rice to herbivores. Using this method, by quantifying the induction of chemicals for GUS activity in a specific screening system that we established previously, 5 candidate elicitors were selected from the 29 designed and synthesized phenoxyalkanoic acid derivatives. Bioassays confirmed that these candidate elicitors could induce plant defense and then repel feeding of white-backed planthopper Sogatella furcifera.
