405-79-8Relevant articles and documents
Modulation of DNA damage response by targeting ATM kinase using newly synthesized di-phenoxy acetamide (DPA) analogs to induce anti-neoplasia
Al-Ostoot, Fares Hezam,Sherapura, Ankith,Malojirao, Vikas H.,Thirusangu, Prabhu,Al-Muhimeed, Tahani I.,Khanum, Shaukath Ara,Prabhakar
, p. 1344 - 1360 (2021/06/14)
Background: Imbalance and instability in the structure of the DNA have become major characteristics of cancer. In response to DNA damage, DNA damage response (DDR) protein, ataxia telangiectasia mutated (ATM), plays a pivotal role in the modulation of regulatory regions responsible for inhibition of apoptosis, thereby neoplastic progression. Methods: A new series of DPA (7a–t) were synthesized, characterized. Anti-proliferative studies to identify the lead compound were carried out by LDH and MTT assay. Apoptosis/DNA damage was measured through FACS, Annexin-v staining, TUNEL and Comet assay. Elucidation of molecular mechanism through immunoblot and further validation of the drug effect through in vivo approaches. Results: Initial in vitro anti-proliferative screening of Compounds DPA (7a–t) against multiple cancer cell lines identified Compound DPA (7n) as a potent cytotoxic molecule with IC50 value of 4.3?μM. Down the line, in vitro and in vivo evaluation of Compound DPA (7n) inferred that it has apoptotic inducing potentiality. Further, evaluation of molecular mechanism inferred that Compound DPA (7n) effectively modulates ATM phosphorylation only, eventually altering downstream signalling pathways. Conclusions: Compound DPA (7n) emerged as a potent proapoptotic and anti-neoplastic agent by inhibiting ATM kinase activity both in vitro and in vivo. The conferring results ascertain that the drug could be developed as a new ATM kinase inhibitor with anti-cancer capacity. Graphic abstract: [Figure not available: see fulltext.]
ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE 1 (ENPP1) MODULATORS AND USES THEREOF
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, (2021/07/02)
Provided herein are small molecule modulators of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.
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.
