The Experts below are selected from a list of 9 Experts worldwide ranked by ideXlab platform
Guangyu Zhu - One of the best experts on this subject based on the ideXlab platform.
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a monofunctional platinum ii based anticancer agent from a Salicylanilide Derivative synthesis antiproliferative activity and transcription inhibition
Journal of Inorganic Biochemistry, 2015Co-Authors: Beilei Wang, Zhigang Wang, Wai Kin Tang, Guangyu ZhuAbstract:Abstract Cationic monofunctional platinum(II)-based anticancer agents with a general formula of cis -[Pt(NH 3 ) 2 (N-donor)Cl] + have recently drawn significant attention due to their unique mode of action, distinctive anticancer spectrum, and promising antitumor activity both in vitro and in vivo . Understanding the mechanism of action of novel monofunctional platinum compounds through rational drug design will aid in the further development of active agents. In this study, we synthesized and evaluated a monofunctional platinum-based anticancer agent SA–Pt containing a bulky Salicylanilide moiety. The antiproliferative activity of SA–Pt was close to that of cisplatin. Mechanism studies revealed that SA–Pt entered HeLa cells more efficiently than cisplatin, blocked the cell cycle at the S-phase, and induced apoptosis. The compound bound to DNA as effectively as cisplatin, but did not block RNA polymerase II-mediated transcription as strongly as cisplatin, indicating that once the compound formed Pt-DNA lesions, the Salicylanilide group was more easily recognized and removed. This study not only enriches the family of monofunctional platinum-based anticancer agents but also guides the design of more potent monofunctional platinum complexes.
Beilei Wang - One of the best experts on this subject based on the ideXlab platform.
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a monofunctional platinum ii based anticancer agent from a Salicylanilide Derivative synthesis antiproliferative activity and transcription inhibition
Journal of Inorganic Biochemistry, 2015Co-Authors: Beilei Wang, Zhigang Wang, Wai Kin Tang, Guangyu ZhuAbstract:Abstract Cationic monofunctional platinum(II)-based anticancer agents with a general formula of cis -[Pt(NH 3 ) 2 (N-donor)Cl] + have recently drawn significant attention due to their unique mode of action, distinctive anticancer spectrum, and promising antitumor activity both in vitro and in vivo . Understanding the mechanism of action of novel monofunctional platinum compounds through rational drug design will aid in the further development of active agents. In this study, we synthesized and evaluated a monofunctional platinum-based anticancer agent SA–Pt containing a bulky Salicylanilide moiety. The antiproliferative activity of SA–Pt was close to that of cisplatin. Mechanism studies revealed that SA–Pt entered HeLa cells more efficiently than cisplatin, blocked the cell cycle at the S-phase, and induced apoptosis. The compound bound to DNA as effectively as cisplatin, but did not block RNA polymerase II-mediated transcription as strongly as cisplatin, indicating that once the compound formed Pt-DNA lesions, the Salicylanilide group was more easily recognized and removed. This study not only enriches the family of monofunctional platinum-based anticancer agents but also guides the design of more potent monofunctional platinum complexes.
Zhigang Wang - One of the best experts on this subject based on the ideXlab platform.
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a monofunctional platinum ii based anticancer agent from a Salicylanilide Derivative synthesis antiproliferative activity and transcription inhibition
Journal of Inorganic Biochemistry, 2015Co-Authors: Beilei Wang, Zhigang Wang, Wai Kin Tang, Guangyu ZhuAbstract:Abstract Cationic monofunctional platinum(II)-based anticancer agents with a general formula of cis -[Pt(NH 3 ) 2 (N-donor)Cl] + have recently drawn significant attention due to their unique mode of action, distinctive anticancer spectrum, and promising antitumor activity both in vitro and in vivo . Understanding the mechanism of action of novel monofunctional platinum compounds through rational drug design will aid in the further development of active agents. In this study, we synthesized and evaluated a monofunctional platinum-based anticancer agent SA–Pt containing a bulky Salicylanilide moiety. The antiproliferative activity of SA–Pt was close to that of cisplatin. Mechanism studies revealed that SA–Pt entered HeLa cells more efficiently than cisplatin, blocked the cell cycle at the S-phase, and induced apoptosis. The compound bound to DNA as effectively as cisplatin, but did not block RNA polymerase II-mediated transcription as strongly as cisplatin, indicating that once the compound formed Pt-DNA lesions, the Salicylanilide group was more easily recognized and removed. This study not only enriches the family of monofunctional platinum-based anticancer agents but also guides the design of more potent monofunctional platinum complexes.
Wai Kin Tang - One of the best experts on this subject based on the ideXlab platform.
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a monofunctional platinum ii based anticancer agent from a Salicylanilide Derivative synthesis antiproliferative activity and transcription inhibition
Journal of Inorganic Biochemistry, 2015Co-Authors: Beilei Wang, Zhigang Wang, Wai Kin Tang, Guangyu ZhuAbstract:Abstract Cationic monofunctional platinum(II)-based anticancer agents with a general formula of cis -[Pt(NH 3 ) 2 (N-donor)Cl] + have recently drawn significant attention due to their unique mode of action, distinctive anticancer spectrum, and promising antitumor activity both in vitro and in vivo . Understanding the mechanism of action of novel monofunctional platinum compounds through rational drug design will aid in the further development of active agents. In this study, we synthesized and evaluated a monofunctional platinum-based anticancer agent SA–Pt containing a bulky Salicylanilide moiety. The antiproliferative activity of SA–Pt was close to that of cisplatin. Mechanism studies revealed that SA–Pt entered HeLa cells more efficiently than cisplatin, blocked the cell cycle at the S-phase, and induced apoptosis. The compound bound to DNA as effectively as cisplatin, but did not block RNA polymerase II-mediated transcription as strongly as cisplatin, indicating that once the compound formed Pt-DNA lesions, the Salicylanilide group was more easily recognized and removed. This study not only enriches the family of monofunctional platinum-based anticancer agents but also guides the design of more potent monofunctional platinum complexes.
Hsu Shan Huang - One of the best experts on this subject based on the ideXlab platform.
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lcc 09 a novel Salicylanilide Derivative exerts anti inflammatory effect in vascular endothelial cells
Journal of Inflammation Research, 2021Co-Authors: Ramcharan Singh Angom, Jian Zhu, Maryam Rachmawati Sumitra, Victoria Pham, Shamit K Dutta, Enfeng Wang, Vijay Sagar Madamsetty, Gabriel D Perezcordero, Hsu Shan HuangAbstract:Objective Endothelial cell (EC) activation facilitates leukocyte adhesion to vascular walls, which is implicated in a variety of cardiovascular diseases and is a target for prevention and treatment. Despite the development of anti-inflammatory medications, cost-effective therapies with significant anti-inflammatory effects and lower organ toxicity remain elusive. The goal of this study is to identify novel synthetic compounds that inhibit EC inflammatory response with minimal organ toxicity. Methods and results In this study, we discovered LCC-09, a Salicylanilide Derivative consisting of the functional fragment of magnolol, 2,4-difluorophenyl, and paeonol moiety of salicylate, as a novel anti-inflammatory compound in cultured ECs and zebrafish model. LCC-09 was shown to inhibit pro-inflammatory cytokine tumor necrosis factor-α (TNFα)-induced expression of adhesion molecules and inflammatory cytokines, leading to reduced leukocyte adhesion to ECs. Mechanistically, LCC-09 inhibits the phosphorylation of signal transducer and activator of transcription 1 (STAT1), TNFα-induced degradation of NF-κ-B Inhibitor-α (IκBα) and phosphorylation of NFκB p65, resulting in reduced NFκB transactivation activity and binding to E-selectin promoter. Additionally, LCC-09 attenuated TNFα-induced generation of reactive oxygen species in ECs. Molecular docking models suggest the binding of LCC-09 to NFκB essential modulator (NEMO) and Janus tyrosine kinase (JAK) may lead to dual inhibition of NFκB and STAT1. Furthermore, the anti-inflammatory effect of LCC-09 was validated in the lipopolysaccharides (LPS)-induced inflammation model in zebrafish. Our results demonstrated that LCC-09 significantly reduced the LPS-induced leukocyte recruitment and mortality of zebrafish embryos. Finally, LCC-09 was administered to cultured ECs and zebrafish embryos and showed minimal toxicities. Conclusion Our results support that LCC-09 inhibits EC inflammatory response but does not elicit significant toxicity.
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a novel Salicylanilide Derivative induces autophagy cell death in castration resistant prostate cancer via er stress activated perk signaling pathway
Molecular Cancer Therapeutics, 2020Co-Authors: Chia Ling Hsieh, Hsu Shan Huang, Kuan Chou Chen, Teigi Saka, Chih Ying Chiang, Leland W K Chung, Shian Ying SungAbstract:Metastatic castration-resistant prostate cancer (CRPC) is currently incurable. Cancer growth and progression is intimately affected by its interaction with host microenvironment. Cotargeting of the stroma and prostate cancer is therefore an emerging therapeutic strategy for metastatic CRPC. Cancer-induced osteoclastogenesis is known to contribute to CRPC bone metastasis. This study is to extend pharmacologic value of our synthesized LCC03, a Derivative of 5-(2',4'-difluorophenyl)-Salicylanilide that has previously testified for its osteoclastogenesis activity, by exploring its additional cytotoxic properties and underlying mechanism in CRPC cells. LCC03 was chemically synthesized and examined for cell growth inhibition in a serial of CRPC cell lines. We demonstrated that LCC03 dose-dependently suppressed proliferation and retarded cell-cycle progression in CRPC cells. The classical autophagy features, including autophagosome formation and LC3-II conversion, were dramatically shown in LCC03-treated CRPC cells, and it was associated with the suppressed AKT/mTOR signaling pathways, a major negative regulator of autophagy. Moreover, an expanded morphology of the endoplasmic reticulum (ER), increased expression of the ER stress markers GRP78 and PERK, and eIF2α phosphorylation were observed. Blockage of autophagy and PERK pathways using small molecule inhibitors or shRNA knockdown reversed LCC03-induced autophagy and cell death, thus indicating that the PERK-eIF2α pathway contributed to the LCC03-induced autophagy. Furthermore, treatment of tumor-bearing mice with intraperitoneal administered LCC03 suppressed the growth of CRPC xenografts in mouse bone without systemic toxicity. The dual action of 5-(2',4'-difluorophenyl)-Salicylanilide on targeting both the osteoclasts and the tumor cells strongly indicates that LCC03 is a promising anticancer candidate for preventing and treating metastatic CRPC.
