57944-75-9Relevant academic research and scientific papers
Extending the structure?activity relationship study of marine natural ningalin B analogues as P-glycoprotein inhibitors
Yang, Chao,Wong, Iris L.K.,Peng, Kai,Liu, Zhen,Wang, Peng,Jiang, Tingfu,Jiang, Tao,Chow, Larry M.C.,Wan, Sheng Biao
, p. 795 - 806 (2017)
In the present study, a total of 25 novel ningalin B analogues were synthesized and evaluated for their P-gp modulating activity in a P-gp overexpressed breast cancer cell line LCC6MDR. Preliminary structure-activity study shows that A ring and its two methoxy groups are important pharmacophores for P-gp inhibiting activity. Among all derivatives, 23 is the most potent P-gp modulator with EC50of 120–165?nM in reversing paclitaxel, DOX, vinblastine and vincristine resistance. It is relatively safe to use with selective index at least greater than 606 compared to verapamil. Mechanistic study demonstrates that compound 23 reverses P-gp mediated drug resistance by inhibiting transport activity of P-gp, thereby restoring intracellular drug accumulation. In summary, our study demonstrates that ningalin B analogue 23 is a non-cytotoxic and effective P-gp chemosensitizer that can be used in the future for reversing P-gp mediated clinical cancer drug resistance.
Structure-based design of phthalimide derivatives as potential cyclooxygenase-2 (COX-2) inhibitors: Anti-inflammatory and analgesic activities
Alanazi, Amer M.,El-Azab, Adel S.,Al-Suwaidan, Ibrahim A.,Eltahir, Kamal Eldin H.,Asiri, Yousif A.,Abdel-Aziz, Naglaa I.,Abdel-Aziz, Alaa A.-M.
, p. 115 - 123 (2015/02/19)
A group of 30 cyclic imides (1-10a-c) was designed for evaluation as a selective COX-2 inhibitor and investigated in vivo for anti-inflammatory and analgesic activities. Compounds 6a, 6b, 7a and 7b exhibit optimal COX-2 inhibitory potency (IC50 Combining double low line 0.18, 0.24, 0.28 and 0.36 μM; respectively) and selectivity index (SI) range of 363-668. In vitro COX-1/COX-2 inhibition structure-activity studies identified compound 6a as a highly potent (IC50 Combining double low line 0.18 μM), and an extremely selective [COX-2 (SI) Combining double low line 668] comparable to celecoxib [COX-2 (SI) > 384], COX-2 inhibitor that showed superior anti-inflammatory activity (ED50 Combining double low line 54.0 mg/kg) relative to diclofenac (ED50 Combining double low line 114 mg/kg). Molecular Docking study of the synthesized compound 6a into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor. Docking study showed that the methoxy moeities of 6a inserted deep inside the 2°-pocket of the COX-2 active site, where the O-atoms of such groups underwent an H-bonding interaction with His90 (3.02 g.,), Arg513 (1.94, 2.83 g.,), and Gln192 (3.25 g.,).
Prostanoids and related compounds. VII. Synthesis and inhibitory activity of 1-isoindolinone derivatives possessing inhibitory activity against thromboxane A2 analog (U-46619)-induced vasoconstriction
Kato, Yoshiaki,Takemoto, Masumi,Achiwa, Kazuo
, p. 529 - 535 (2007/10/03)
We have synthesized a series of novel 1-isoindolinone derivatives, which inhibited the contraction of pig coronary artery induced by U-46619, a thromboxane A2 analog.
