90002-56-5Relevant articles and documents
Anticancer profile and anti-inflammatory effect of new N-(2-((4-(1,3-diphenyl-1H-pyrazol-4-yl)pyridine sulfonamide derivatives
Abdel-Maksoud, Mohammed S.,Mohamed Hassan, Rasha,Abdel-Sattar El-Azzouny, Aida,Nabil Aboul-Enein, Mohamed,Oh, Chang-Hyun
, (2021/10/25)
A new series of N-(2-((4-(1,3-diphenyl-1H-pyrazol-4-yl)pyridine sulfonamide derivatives 11a-o were designed and synthesized based on our previous works. The new series was tested for its anticancer and anti-inflammatory effects. The anticancer profile of
N-(2-ethylamine) benzenesulfonamide cordycepin derivative as well as preparation method and application thereof
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Paragraph 0030; 0031, (2020/01/25)
The invention discloses an N-(2-ethylamine) benzenesulfonamide cordycepin derivative as well as a preparation method and an application thereof in inhibiting tumor cell proliferation, and the N-(2-ethylamine) benzenesulfonamide cordycepin derivative is pr
Structural optimization of imidazothiazole derivatives affords a new promising series as B-Raf V600E inhibitors; synthesis, in vitro assay and in silico screening
Abdel-Maksoud, Mohammed S.,Ali, Eslam M. H.,Ammar, Usama M.,Ho Yoo, Kyung,Mersal, Karim I.,Oh, Chang-Hyun
, (2020/05/29)
BRAF mutation is commonly known in a number of human cancer types. It is counted as a potential component in treating cancer. In this study, based on structural optimization of previously reported inhibitors (3-fluro substituted derivatives of imidazo[2,1-b]thiazole-based scaffold), we designed and synthesized sixteen new imidazo[2,1-b]thiazole derivatives with m-nitrophenyl group at position 6. The electron withdrawing properties was reserved while the polarity was modified compared to previously synthesized compounds (-F). Furthermore, the new substituted group (–NO2) provided an additional H-bond acceptor(s) which may bind with the target enzyme through additional interaction(s). In vitro cytotoxicity evaluation was performed against human cancer cell line (A375). In addition, in vitro enzyme assay was performed against mutated B-Raf (B-Raf V600E). Compounds 13a, 13g and 13f showed highest activity on mutated B-Raf with IC50 0.021, 0.035 and 0.020 μM. All target compounds were tested for in vitro cytotoxicity against NCI 60 cell lines. Compounds 13a and 13g were selected for 5 doses test mode. Moreover, in silico molecular simulation was explored in order to explore the possible interactions between the designed compounds and the B-Raf V600E active site.
Modification of imidazothiazole derivatives gives promising activity in B-Raf kinase enzyme inhibition; synthesis, in vitro studies and molecular docking
Ammar, Usama M.,Abdel-Maksoud, Mohammed S.,Mersal, Karim I.,Ali, Eslam M.H.,Yoo, Kyung Ho,Choi, Hong Seok,Lee, Jae Kyun,Cha, Sun Young,Oh, Chang-Hyun
supporting information, (2020/08/14)
B-Raf mutation was identified as a key target in cancer treatment. Based on structural features of dabrafenib (potent FDA approved B-Raf inhibitor), the design of new NH2-based imidazothiazole derivatives was carried out affording new highly potent derivatives of imidazothiazole-based scaffold with amino substitution on the terminal phenyl ring as well as side chain with sulfonamide group and terminal substituted phenyl ring. In vitro enzyme assay was investigated against V600E B-Raf kinase. Compounds 10l, 10n and 10o showed higher inhibitory activities (IC50 = 1.20, 4.31 and 6.21 nM, respectively). In vitro cytotoxicity evaluation was assessed against NCI-60 cell lines. Most of tested derivatives showed cytotoxic activities against melanoma cell line. Compound 10k exhibited most potent activity (IC50 = 2.68 μM). Molecular docking study revealed that the new designed derivatives preserved the same binding mode of dabrafenib with V600E B-Raf active site. It was investigated that the new modification in the synthesized derivatives (substituted with NH2) had a significant inhibitory activity towards V600E B-Raf. This core scaffold is considered a key compound for further structural and molecular optimization.
Anticancer profile of newly synthesized BRAF inhibitors possess 5-(pyrimidin-4-yl)imidazo[2,1-b]thiazole scaffold
Abdel-Maksoud, Mohammed S.,Ammar, Usama M.,Oh, Chang-Hyun
, p. 2041 - 2051 (2019/04/05)
In this work, a new series of imidazo[2,1-b]thiazole was designed and synthesized. The new compounds are having 3-fluorophenyl at position 6 of imidazo[2,1-b]thiazole and pyrimidine ring at position 5. The pyrimidine ring containing either amide or sulphonamide moiety attached to a linker (ethyl or propyl) at position 2 of the pyrimidine ring. The final compounds were selected by NCI for in vitro cytotoxicity screening. Most derivatives showed cytotoxic activity against colon cancer and melanoma cell lines. In addition, IC50s of the target compounds were determined over A375 and SK-MEL-28 cell lines using sorafenib as positive control. Compounds12b, 12c, 12e, 12f, 15a, 15d, 15f, 14g and 15h exhibited superior activity when compared to sorafenib. The most potent compounds were tested against wild type BRAF, v600e BRAF, and CRAF. Compound 15h exhibited a potential inhibitory effect againstV600EBRAF (IC50 = 9.3 nM).
Design, synthesis, and anticancer activity of imidazo[2,1-b]oxazole-based RAF kinase inhibitors
Abdel-Maksoud, Mohammed S.,Ammar, Usama M.,El-Gamal, Mohammed I.,Gamal El-Din, Mahmoud M.,Mersal, Karim I.,Ali, Eslam M.H.,Yoo, Kyung Ho,Lee, Kyung-Tae,Oh, Chang-Hyun
, (2019/10/19)
In the present work, a novel series of B-RAF kinase inhibitors having imidazo[2,1-b]oxazole scaffold was designed and synthesized based on the structures of the well-known B-RAF inhibitors. The twenty two final compounds were tested over A375 and SKMEL28 cell lines to determine the primary cytotoxic activity of these compounds, and their activities were compared with that of sorafenib as a standard. Compounds 11c, 11e, 11o, 11q, 11r, and 11u exhibited higher cellular activity compared to sorafenib with IC50 values of 7.25, 8.03, 9.81, 8.47, 4.70, and 9.04 μM, respectively and 10.38 μM for sorafenib. In addition, the target compounds were screened for their anticancer activity by the NCI-60 cell line assay. Compounds 11v and 11u were the most active compounds with percent inhibition reached 95.99% for 11v and 87.03% for 11u over K562 cell line at 10 μM concentration. Compound 11v was selected for 5-dose test mode. Furthermore, the kinase inhibitory activities of 11a, 11c, 11e, 11i, 11o, 11q, 11r, 11u, and 11v were determined against wild-type B-RAF, V600E-B-RAF, and RAF1. Compound 11o was the most potent against V600E-B-RAF with IC50 34 nM followed by 11q and 11u with IC50 92 and 93 nM, respectively.
Aryne-Mediated [2,3]-Sigmatropic Rearrangement of Tertiary Allylic Amines
Zhang, Juan,Chen, Zhi-Xiong,Du, Ting,Li, Bing,Gu, Yonghong,Tian, Shi-Kai
supporting information, p. 4872 - 4875 (2016/10/18)
A new strategy has been established for the [2,3]-sigmatropic rearrangement of quaternary allylic ammonium ylides via in situ activation of tertiary allylic amines with arynes under mild conditions. Using 2-(trimethylsilyl)aryl triflates as aryne precurso