Theoretical model for the design and preparation of a CNT–ursonic acid drug matrix as HIV-gp120 entry inhibitor

Abstract

Abstract Human Immunodeficiency Virus (HIV) which infection results into Acquired Immunodeficiency Syndrome (AIDS) has claimed the lives of one half of its 70 million victims, a deadly disease that has attracted a global concern. Major challenges associated with modern HIV drugs include side effects, drug resistance, toxicity, patient compliance and lack of curative effect, which necessitated the need for urgent discovery of safer, cheaper and effective alternative drugs from natural plants. Currently, HIV-gp120 entry inhibitors are the most explored, based on the finding that the virus binds to the human CD4 cell via V1/V2 and V3 loops of its glycoprotein-120. The conceptual framework of this report is based on the chemistry that an acid anhydride converts proteins into corresponding acetylaminoalkyl methyl ketones by attacking the N- and C-terminals of the molecules in the presence of a base. Relatively, in this report, an acid anhydride, consisting of carbon nanotubes (CNTs) and ursonic acid (UA) backbone (CNT–UA), is theoretically designed and its expected interaction with HIV-glycoprotein-120 predicted. CNTs are first subjected to acid oxidation using a mixture of HNO3/H2SO4 (3:1) to obtain CNT–COOH moieties followed by acylation with thionyl chloride, SOCl2, to produce the more reactive CNT–COCl species. Refluxing resulting acyl chloride with a solution of UA-pyridine is expected to covalently attach the C-28 of the terpene to yield the desired CNT–UA (acid anhydride) drug matrix. The CNT-AU drug in pyridine base is expected to expend its HIV-gp120 entry inhibition via Dakin–West reaction by attacking the VI/V2 and V3 loops of the virus glycoprotein, converting it into a keto amide in the presence of 4-dimethylaminopyridine catalyst. If this model is intensively explored, it may help towards finding a final cure for HIV/AIDS.