Synthesis and Biological Evaluation of Benzophenone Derivatives as Potential HIV-1 Inhibitors

Title:Synthesis and Biological Evaluation of Benzophenone Derivatives as Potential HIV-1 Inhibitors

Volume: 13 Issue: 4

Author(s): Zhendong Song, Ping Wang, Shanshan Huang, Changyuan Wang, Rui-Rui Wang, Liu-Meng Yang, Yuhong Zhen, Kexin Liu, Yong-Tang Zheng*Xiaodong Ma*

Affiliation:

• College of Pharmacy, Dalian Medical University, Dalian 116044,China

• Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223,China

Keywords: Activity, AIDS, analogues, benzophenone, HIV-1, inhibitor.

Abstract: Background: Although a number of agents can achieve high response in acquired immunodeficiency syndrome (AIDS) patients, safer and more active HIV inhibitors are still needed for the growing number of patients infected with resistant HIV virus strains. GW678248 is one of the most potent benzophenone derivatives, exhibiting high potency against a panel of HIV- 1 virus (wild-type, K103N mutant, Y181C, etc.) at 1 nmol/L concentrations. However, the safety issues associated with rash and liver metabolic enzymes ultimately led to discontinue its further deve-lopment. As a continuation of our structural modifications on this template, in this manuscript, a new series of benzophenones are described as potential HIV inhibitors.

Methods: All the title molecules were synthesized according to the routes in Scheme 1 and Scheme 2, and were tested for anti-HIV-1 activity using the MTT method. In the molecular simulation, the docking program of AutoDock 4.0.1 in parallel with the default parameters were used.

Results: A series of novel benzophenone derivatives (BPs) with nanomolar anti-HIV-1 activity were identified. Of these inhibitors, analogue 10i (EC50 = 2.9 nmol/L), the most active inhibitor, was comparable to the lead compound GW678248 in inhibiting the wild-type HIV-1 virus. Additionally, analogue 13b, which not only exhibited strong inhibitory activity against the HIV-1 virus (EC50 = 4.2 nmol/L), but also has very low cytotoxicity with a TI value of more than 219178.1 was also discovered.

Conclusion: This study led to the identification of a series of benzophenone derivatives with nanomolar level of anti-HIV-1 activity. Analogues 10i and 13b, with low cytotoxicity along with high activity are worthy of further development.

Cite this article as:

Song Zhendong, Wang Ping, Huang Shanshan, Wang Changyuan, Wang Rui-Rui, Yang Liu-Meng, Zhen Yuhong, Liu Kexin, Zheng Yong-Tang*, Ma Xiaodong*, Synthesis and Biological Evaluation of Benzophenone Derivatives as Potential HIV-1 Inhibitors, Medicinal Chemistry 2017; 13 (4) . https://dx.doi.org/10.2174/1573406413666161111151814

DOI https://dx.doi.org/10.2174/1573406413666161111151814	Print ISSN 1573-4064
Publisher Name Bentham Science Publisher	Online ISSN 1875-6638