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Labdane analogs with o-quinol, catechol and hydroquinone moiety have been synthesized using Diels-Alder reaction of methyl 3,4-dioxocyclohexa-1,5-diene-carboxylate, 3,4-dioxocyclohexa-1,5-diene-carboxylic acid and 3,6-dioxocyclohexa-1,4-dienecarboxylic acid with mono terpene 1,3-dienes, namely ocimene and myrcene. The resulting molecules and their derivatives were evaluated for their anti-HIV-1 activity using TZM-bl cell based virus infectivity assay. Two molecules 13 and 18 showed anti-HIV activity with IC50 values 5.0 (TI=11) and 4.6 (TI=46)µM, respectively. The compounds 17, 18 and 20 showed efficacy against HIV-1 integrase activity and showed inhibition with IC50 13.4, 11.1 and 11.5µM, respectively. The HIV-1 integrase inhibition activity of these synthetic molecules was comparable with integric acid, the natural fungal metabolite. Molecular modeling studies for the HIV-1 integrase inhibition of these active synthetic molecules indicated the binding to the active site residues of the enzyme.

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BACKGROUND: In the present study, extracts prepared from the leaves of Rhus parviflora Roxb. (Anacardiaceae) were evaluated for their anti-HIV activity, which have been traditionally used for the treatment of neurological disorders such as anxiety, insomnia and epilepsy. METHODS: Aqueous and 50% ethanolic extracts prepared from leaves of the plant were tested for their cytotoxicity and anti-HIV property using reporter gene based assays as well as human peripheral blood lymphocytes (PBLs). Further these extracts were evaluated for their ability to inhibit HIV-1 reverse transcriptase (RT) and protease activity. Safety profile of the extracts was determined on viability of Lactobacillus sp., secretion of pro-inflammatory cytokines by vaginal keratinocytes and transepithelial resistance. RESULTS: Both aqueous (IC50 = 15 µg/ml) and 50% ethanolic (IC50 = 26 µg/ml) extracts prepared from leaves of R. parviflora showed anti-HIV activity in TZM-bl cells wherein the virus was treated with the extracts prior to infection. Further, both the extracts also inhibited virus load in HIV infected CEM-GFP cells and human PBLs. The anti-HIV activity is mediated through inhibition of HIV-1 protease activity. Both the extracts did not disturb the integrity of monolayer formed by intestinal epithelial Caco-2 cells. The extracts when tested up to 100 µg/ml did not significantly reduce the viability of L. plantarum, L. fermentum, L. rhamnosus and L. casei. The extracts (100 µg/ml) did not reveal any cytotoxic effect on vaginal keratinocytes (Vk2/E6E7). Levels of pro-inflammatory cytokines secreted by Vk2/E6E7 cells treated with both the plant extracts were within the non-inflammatory range. CONCLUSIONS: The studies reported herein showed in vitro anti-HIV activity and preliminary safety profile of the extracts prepared from the leaves of R. parviflora.

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Sericostoma pauciflorum Stocks ex Wight (Family Boraginaceae) used against cancer, diabetes and known to be health promoter. Callus cultures have been established from the stem explants on Murashige and Skoog (MS) medium supplemented with 1.5 mg/L concentration of different growth hormone viz. kinetin (Kn), indole 3-acetic acid (IAA) and indole 3-butyric acid (IBA). At 6 weeks of age, these calli were harvested, dried and extracted successively in pet, ether, methanol and water. Extracts were dried, weighed (%) and analyzed for their bioefficacies. Antimicrobial activities were determined using agar well diffusion and antioxidant potentials by DPPH and FRAP methods. Among all the test extracts, the extract of stem callus raised on IBA found to be more effective whereas it's pet. ether extract showed appreciable activity against both the test bacteria and fungi (S. aureus- IZ 14.00 ± 0.57 mm and T. rubrum- 16.33 ± 0.32 mm), followed by methanol extract (S. aureus- IZ 13.00 ± 0.57 mm, A. niger and P. chrysogenum- IZ 16.66 mm in both). In antioxidant potentials, all aqueous extracts were more active where IBA and Kn extracts demonstrated 0.06 mg/mL IC50 value (% inhibition 93.30 and 92.70 respectively at 0.8 mg/mL concentration) with 366 ± 6.69 and 343 ± 3.34 ascorbic acid equivalent antioxidant potentials at 1 mg/mL concentration. Furthermore, the chemical profile of test extracts was carried out. The bioactive secondary metabolites, ß-sitosterol and caffeic acid was isolated from culture tissue of 6 weeks-old callus, and their identification and confirmation was carried out by color reaction, TLC behavior and IR spectrum techniques.