New Genetic Bomb Trigger: Design, Synthesis, Molecular Dynamics Simulation, and Biological Evaluation of Novel BIBR1532-Related Analogs Targeting Telomerase against Non-Small Cell Lung Cancer was written by Tawfik, Haytham O.;El-Hamaky, Anwar A.;El-Bastawissy, Eman A.;Shcherbakov, Kirill A.;Veselovsky, Alexander V.;Gladilina, Yulia A.;Zhdanov, Dmitry D.;El-Hamamsy, Mervat H.. And the article was included in Pharmaceuticals in 2022.Computed Properties of C12H16N2O This article mentions the following:
Telomeres serve a critical function in cell replication and proliferation at every stage of the cell cycle. Telomerase is a ribonucleoprotein, responsible for maintaining the telomere length and chromosomal integrity of frequently dividing cells. Although it is silenced in most human somatic cells, telomere restoration occurs in cancer cells because of telomerase activation or alternative telomere lengthening. The telomerase enzyme is a universal anticancer target that is expressed in 85-95% of cancers. BIBR1532 is a selective non-nucleoside potent telomerase inhibitor that acts by direct noncompetitive inhibition. Relying on its structural features, three different series were designed, and 30 novel compounds were synthesized and biol. evaluated as telomerase inhibitors using a telomeric repeat amplification protocol (TRAP) assay. Target compounds 29a, 36b, and 39b reported the greatest inhibitory effect on telomerase enzyme with IC50 values of 1.7, 0.3, and 2.0 渭M, resp., while BIBR1532 displayed IC50 = 0.2 渭M. Compounds 29a, 36b, and 39b were subsequently tested using a living-cell TRAP assay and were able to penetrate the cell membrane and inhibit telomerase inside living cancer cells. Compound 36b was tested for cytotoxicity against 60 cancer cell lines using the NCI (USA) procedure, and the % growth was minimally impacted, indicating telomerase enzyme selectivity. To investigate the interaction of compound 36b with the telomerase allosteric binding site, mol. docking and mol. dynamics simulations were used. In the experiment, the researchers used many compounds, for example, 4-(4-Methylpiperazin-1-yl)benzaldehyde (cas: 27913-99-1Computed Properties of C12H16N2O).
4-(4-Methylpiperazin-1-yl)benzaldehyde (cas: 27913-99-1) belongs to piperazine derivatives. The piperazine scaffold is often found in biologically active compounds in different therapeutic areas. These therapeutic areas include antifungals, antidepressants, antivirals, and serotonin receptor (5-HT) antagonists/agonists. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Computed Properties of C12H16N2O
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics