Gao-yun Hu

Name:

Organization: Central South University

Department: Department of Medicinal Chemistry, School of Pharmacy

Title:

Chemicals
References

Synthesis, Pharmacophores, and Mechanism Study of Pyridin-2(1H)-one Derivatives as Regulators of Translation Initiation Factor 3A

Co-reporter:Weixing Zhu;Jie Shen;Qianbin Li;Qi Pei;Jun Chen;Zhuo Chen;Zhaoqian Liu;Gaoyun Hu

Archiv der Pharmazie 2013 Volume 346( Issue 9) pp:654-666

Publication Date(Web):

DOI:10.1002/ardp.201300138

Twenty-seven 1,5-disubstituted-pyridin-2(1H)-one derivatives were synthesized and evaluated for their anti-cancer and anti-fibrosis activity by A549 and NIH3T3 cell viability assays, respectively. To study the selectivity between the cancer and fibrosis cell lines, pharmacophore models (F₁–F₄) were built in advance for compounds with pyridin-2(1H)-one scaffold, which revealed the relationship between the occupation of the aromatic sub-site F₄ and potent anti-cancer activity. The relationship between structure and anti-cancer activity for all target compounds is also reported herein: 1-Phenyl-5-((m-tolylamino)methyl)pyridine-2(1H)-one (22) displayed both potency and selectivity (IC₅₀ = 0.13 mM) toward the A549 cell line through the inhibition of translation initiation, especially by eIF3a suppression, and can be treated as a lead for the design of novel eIF3a regulators and anti-lung cancer agents.

Synthesis, Pharmacokinetics, and Pharmacodynamics Studies of Valsartan Peptide Derivatives

Co-reporter:Chun Wu;Yanpeng Hu;Qianbin Li;Limei He;Jun Chen;Zeneng Cheng;Yuanjian Li;Gaoyun Hu

Archiv der Pharmazie 2012 Volume 345( Issue 5) pp:393-400

Publication Date(Web):

DOI:10.1002/ardp.201100377

Abstract

In order to increase the intestinal permeability of valsartan, 14 esters and peptide derivatives of valsartan were chemically synthesized and their absorption characteristics were described. All derivatives were stable and could be better absorbed into the small intestine than valsartan. There are two barriers for the absorption of valsartan derivatives. The elongated half-life (t_1/2) and stable blood concentrations for compound 4 due to the hydrolysis of the ester group in the second barrier were demonstrated in pharmacokinetic experiments. Furthermore, compound 4 also displayed modest anti-hypertension activity in vivo, which makes structural modification of valsartan, especially for the purpose of improvement of its intestinal permeability, valuable for further studies.

Synthesis and structure–activity relationship of 5-substituent-2(1H)-pyridone derivatives as anti-fibrosis agents

Co-reporter:Jun Chen, Miao-Miao Lu, Bin Liu, Zhuo Chen, Qian-Bin Li, Li-Jian Tao, Gao-Yun Hu

Bioorganic & Medicinal Chemistry Letters 2012 Volume 22(Issue 6) pp:2300-2302

Publication Date(Web):15 March 2012

DOI:10.1016/j.bmcl.2012.01.073

Pyridone compounds, such as pirfenidone (PFD) and fluorofenidone (AKF-PD), are multi-target anti-fibrotic agents. Using PFD and AKF-PD as the leading compounds, two series of novel (5-substituent)-2(1H)-pyridone compounds were synthesized with the purpose of maintaining multi-targeting property and overcoming the drawbacks of fast metabolism. These derivatives demonstrated good proliferation inhibiting activity against NIH3T3 cells by MTT assay with AKF-PD as the positive control. Compound 5b exhibited a high potent of anti-fibrosis with a IC50 of 0.08 mmol/L about 34 times of AKF-PD. The SAR of pyridone derivatives as anti-fibrosis agents was also discussed.The potent of compound 5b was about as 34 times as fluorofenidone on inhibiting the NIH3T3 cell.

Therapeutic strategies of diabetic nephropathy: recent progress and future perspectives

Co-reporter:Meng Lv, Zhuo Chen, Gaoyun Hu, Qianbin Li

Drug Discovery Today (March 2015) Volume 20(Issue 3) pp:332-346

Publication Date(Web):1 March 2015

DOI:10.1016/j.drudis.2014.10.007

•The pathogenesis of diabetic nephropathy is described.•Available anti-DN agents with different status are summarized.•The multi-link-targeted agents are potential treatments for DN.Diabetic nephropathy (DN) is one of the most common complications of diabetes with high mortality rates worldwide. The treatment of DN has posed a formidable challenge to the scientific community. Simple control of risk factors has been insufficient to cope with the progression of DN. During the process of anti-DN drug discovery, multiple pathogeneses such as oxidative stress, inflammation and fibrosis should all be considered. In this review, the pathogenesis of DN is summarized. The major context focuses on a few small molecules toward the pathogenesis available in animal models and clinical trials for the treatment of DN. The perspectives of novel anti-DN agents and the future directions for the prevention of DN are discussed.