152793-23-2Relevant academic research and scientific papers
Design and synthesis of certain substituted cycloalkanecarboxamides structurally related to safinamide with anticonvulsant potential
Aboul-Enein, Mohamed N.,El-Azzouny, Aida A.,Maklad, Yousreya A.,Ismail, Mohamed A.,Ismail, Nasser S. M.,Hassan, Rasha M.
, p. 3767 - 3791 (2015)
A series of novel safinamide derivatives were synthesized and biologically evaluated for their anticonvulsant activity against maximal electroshock seizure assay and subcutaneous pentylenetetrazole (s.c. PTZ) screening test. Compound 13b is the most active derivative in s.c. PTZ screening test with an ED50 value lower than that of safinamide by about tenfold. A molecular modeling study, including fitting to sodium channel blockers 3D-pharmacophore model and docking into a branched-chain aminotransferase enzyme active site were consistent with the in vivo results.
Discovery of 4-benzyloxy and 4-(2-phenylethoxy) chalcone fibrate hybrids as novel PPARα agonists with anti-hyperlipidemic and antioxidant activities: Design, synthesis and in vitro/in vivo biological evaluation
Hassan, Rasha M.,Aboutabl, Mona E.,Bozzi, Manuela,El-Behairy, Mohammed F.,El Kerdawy, Ahmed M.,Sampaolese, Beatrice,Desiderio, Claudia,Vincenzoni, Federica,Sciandra, Francesca,Ghannam, Iman A.Y.
, (2021/08/03)
In the current work, a series of novel 4-benzyloxy and 4-(2-phenylethoxy) chalcone fibrate hybrids (10a-o) and (11a-e) were synthesized and evaluated as new PPARα agonists in order to find new agents with higher activity and fewer side effects. The 2-propanoic acid derivative 10a and the 2-butanoic acid congener 10i showed the best overall PPARα agonistic activity showing Emax% values of 50.80 and 90.55%, respectively, and EC50 values of 8.9 and 25.0 μM, respectively, compared to fenofibric acid with Emax = 100% and EC50 = 23.22 μM, respectively. These two compounds also stimulated carnitine palmitoyltransferase 1A gene transcription in HepG2 cells and PPARα protein expression. Molecular docking simulations were performed for the newly synthesized compounds to study their predicted binding pattern and energies in PPARα active site to rationalize their promising activity. In vivo, compounds 10a and 10i elicited a significant hypolipidemic activity improving the lipid profile in triton WR-1339-induced hyperlipidemic rats, including serum triglycerides, total cholesterol, LDL, HDL and VLDL levels. Compound 10i possessed better anti-hyperlipidemic activity than 10a. At a dose of 200 mg/kg, it demonstrated significantly lower TC, TG, LDL and VLDL levels than that of fenofibrate at the same dose with similar HDL levels. Compounds 10i and 10a possessed atherogenic indices (CRR, AC, AI, CRI-II) like that of fenofibrate. Additionally, a promising antioxidant activity indicated by the increased tissue reduced glutathione and plasma total antioxidant capacity with decreased plasma malondialdehyde levels was demonstrated by compounds 10a and 10i. No histopathological alterations were recorded in the hepatic tissue of compound 10i (200 mg/kg).
Design, synthesis, and biological evaluation of 5-aminotetrahydroquinoline-based LSD1 inhibitors acting on Asp375
Yan, Jiangkun,Gu, Yanting,Sun, Yixiang,Zhang, Ziheng,Zhang, Xiangyu,Wang, Xinran,Wu, Tianxiao,Zhao, Dongmei,Cheng, Maosheng
, (2021/05/17)
The abnormal expression of lysine-specific histone demethylase 1 (LSD1) is associated with different cancer types, and LSD1?inhibitory activity seems to have high therapeutic potential in cancer treatment. Here, we report the design, synthesis, and biochemical evaluation of novel 5-aminotetrahydroquinoline-based LSD1 inhibitors. Among them, compounds A6, A8, B1–B5, and C4 showed preferable inhibitory effects on LSD1, with IC50 = 0.19–0.82 μM. Several potent compounds were selected to evaluate their antiproliferative activity on A549 cells and MCF-7 cells with a high expression of LSD1. The potential binding modes of the compounds were revealed through molecular docking to rationalize the potency of compounds toward LSD1. Our data recognized that the 5-aminotetrahydroquinoline scaffold may serve as a starting point for developing potent LSD1 inhibitors for cancer therapy.
Design, synthesis and biological evaluation of tetrahydroquinoline-based reversible LSD1 inhibitors
Cheng, Maosheng,Jiang, Qinwen,Wang, Jiming,Wang, Xinran,Yan, Jiangkun,Zhang, Cai,Zhang, Xiangyu,Zhao, Dongmei,Zhao, Liyu
, (2020/03/30)
The targeted regulation of LSD1, which is highly expressed in a variety of tumor cells, is a promising cancer therapy strategy. Several LSD1 inhibitors are currently under clinical evaluation, and most of these inhibitors are irreversible. Here, we report the design, synthesis and biochemical evaluation of novel tetrahydroquinoline-based reversible LSD1 inhibitors. Compounds 18s and 18x, which are selective to LSD1 over MAO-A/B, exhibit excellent LSD1 inhibition at the molecular levels with IC50 = 55 nM and 540 nM, respectively. The classic Lineweaver–Burk plots revealed that compound 18s could reversibly bind the LSD1 enzyme in a noncompetitive manner. Molecular docking was used to reveal the potential binding-mode of the compounds and interpret the structure-activity relationships. Furthermore, compounds 18s and 18x significantly inhibited proliferation (IC50 = 1.13 μM and 1.15 μM, respectively) and induced apoptosis in MGC-803 cells with high expression of LSD1. Compound 18x showed acceptable liver microsomal stability. Meanwhile, 18x did not appear to inhibit CYPs at 10 μM in vitro. Remarkably, the oral administration of compound 18x can inhibit the growth of MGC-803 xenograft tumors without significant side effects. Our findings suggest that tetrahydroquinoline-based LSD1 inhibitors deserve further investigation for the treatment of LSD1 overexpressing cancer.
85. Development of Luminescent Europium(III) and Terbium(III) Chelates of 2,2':6',2''-Terpyridine Derivatives for Protein Labelling
Mukkala, Veli-Matti,Helenius, Matti,Hemmilae, Ilkka,Kankare, Jouko,Takalo, Harri
, p. 1361 - 1378 (2007/10/02)
The synthesis and luminescence properties are reported for 20 different chelates composed of 2,2':6',2''-terpyridine as the energy-absorbing and donating group, Eu(III) and Tb(III) as the emitting ions, methylenenitrilo(acetic acids) as the stable chelate
