Biological effects and activity optimization of small-molecule, drug-like synthetic anion transporters.

The balance of normal anion concentrations in cells provides basis for maintaining cellular morphology and function. Disrupting the homeostasis of cellular anions and lysosomal pH, in particular with high selectivity for cancer cells over normal cells may serve as a promising approach for the treatment of cancers. Small-molecule organic compounds with transmembrane anion transport activity, namely synthetic anion transporters are able to destroy the homeostasis of cellular anions, in particular chloride anions to trigger cell death and thus may be developed as a new class of anti-tumor drugs.

A natural theaflavins preparation inhibits HIV-1 infection by targeting the entry step: potential applications for preventing HIV-1 infection.

Theaflavins are the major components of tea polyphenols in brewed black tea. We previously reported that theaflavin derivatives, such as TF3, inhibited HIV-1 entry by targeting gp41. However, it is difficult to purify the individual theaflavins and the purified compounds are highly unstable.

[Inhibition of HIV-1 mediated cell-cell fusion by saponin fraction from Psidium guajava leaf].

Objective: To investigate the effects of the total saponin of Psidium guajava leaf (TSGL) on HIV-1 envelop proteins (env) mediated virus entry into target cells.

Methods: The TSGL was purified and concentrated using SA-1 macropore resin. The effect of TSGL on HIV-1 entry into target cells was tested using a cell-cell fusion assay by mixing CHO-WT and MT-2 cells.

[A non-infectious and quantitative cell-based bioassay for screening HIV entry inhibitors targeting HIV envelope proteins].

Objective: To develop an objective bioassay for quantitative detection of HIV-induced cell-cell fusion for screening HIV entry inhibitors.

Methods: HL2/3 cells expressing HIV envelope proteins gp120/gp41, Tat, and other HIV proteins were co-cultured with HeLa-CD4-LTR-beta-gal cells expressing CD4 receptor and HIV LTR triggered reporter gene beta-galactosidase. The enzyme activities of beta-galactosidase were detected by a chromogenic substrate, chlorophenol red-beta-galactopyranoside (CPRG).

[Study of the mechanism of caffeoyl glucopyranoses in inhibiting HIV-1 entry using pseudotyped virus system].

Objective: To investigate the inhibitory activities of caffeoyl glucopyranoses purified from Balanophora japonica Makino on HIV entry and their mechanism.

Methods: HIV-1 Env pseudovirus was used to evaluate the anti-HIV-1 activity of those compounds. ELISA and molecular docking were used to study the mechanism of the actions of the active compounds.

ADS-J1 inhibits human immunodeficiency virus type 1 entry by interacting with the gp41 pocket region and blocking fusion-active gp41 core formation.

We previously identified a small-molecule anti-human immunodeficiency virus type 1 (anti-HIV-1) compound, ADS-J1, using a computer-aided molecular docking technique for primary screening and a sandwich enzyme-linked immunosorbent assay (ELISA) as a secondary screening method. In the present study, we demonstrated that ADS-J1 is an HIV-1 entry inhibitor, as determined by a time-of-addition assay and an HIV-1-mediated cell fusion assay. Further mechanism studies confirmed that ADS-J1 does not block gp120-CD4 binding and exhibits a marginal interaction with the HIV-1 coreceptor CXCR4.