New Dipterocarpol-Based Molecules with α-Glucosidase Inhibitory and Hypoglycemic Activity.

Dammarane triterpenoids are affordable and bioactive natural metabolites with great structural potential, which makes them attractive sources for drug development. The aim of the study was to investigate the potency of new dipterocarpol derivatives for the treatment of diabetes. Two dammaranes (dipterocarpol and its 20(24)-diene derivative) were modified by a Claisen-Schmidt aldol condensation to afford C2(E)-arylidenes in good yields. The majority of the synthesized compounds exhibited an excellent-to-moderate inhibitory effect toward α-glucosidase (from S. saccharomyces), among them eight compounds showed IC50 values less than 10 µM. 3-Oxo-dammarane-2(E)-benzylidenes (holding p-hydroxy- 3 l and p-carbonyl- 3 m substituents) demonstrated the most potent α-glucosidase inhibition with IC50 0.753 and 0.204 µM, being 232- and 857-times more active than acarbose (IC50 174.90 µM), and a high level of NO inhibition in Raw 264.7 cells with IC50 of 1.75 and 4.57 µM, respectively. An in vivo testing of compound 3 m (in a dose of 20 mg/kg) on a model of streptozotocin-induced T1DM in rats showed a pronounced hypoglycemic activity, the ability to reduce effectively the processes of lipid peroxidation in liver tissue and decrease the excretion of glucose and pyruvic acid in the urine. Compound 3 m reduced the death of diabetic rats and preserved their motor activity.

Allobetulone rearrangement to l8αH,19ßH-ursane triterpenoids with antiviral activity.

Allobetulone E-ring rearrangement under treating with HClO4 in Ac2O under reflux afforded new triterpenoids: 3,28-diacetoxy-21-acetyl-2(3),20(21)-18α,19ßH-ursandiene 3 and 3,28-diacetoxy-2(3),18(19)-oleandiene 4. 18α,19ßH-Ursanes were transformed at A- and E-rings into indolo- and bis-furfurylidene 7 derivatives. Structure elucidation was performed using COSY, NOESY, HSQC and HMBC experiments, and X-Ray analysis for 3. The potential of newly obtained 18α,19ßH-ursanes was evaluated against HCMV and HPV-11, the NCI-60 cancer cell panel and inhibition of α-glucosidase. All of the compounds have shown viral inhibition towards HCMV compared to standard drug Acyclovir. 3ß-Acetoxy-21ß-acetyl-20ß,28-epoxy-18α,19ßН-ursane 1 showed moderate activity (EC50 4.87 µM) towards the HCMV-resistant isolate (GDGr K17) compared to standard drug Cidofovir and was four times more potent than Ganciclovir. Compound 7 inhibited the cell growth of the three melanoma and one colon cancer cell. 3-Oxo-21ß-acetyl-20ß,28-epoxy-18α,19ßН-ursane 5 and compound 7 inhibited α-glucosidase with IC50 28.0 µM and 4.0 µM being from 6 to 44 times more active than acarbose.

Synthesis of messagenin and platanic acid chalcone derivatives and their biological potential.

The chalcone derivatives of 20-oxo-lupanes have been synthesised and screened for some types of biological activity. Ozonolysis of lupanes afforded 20-oxo-derivatives with the following condensation using different aromatic aldehydes by Claisen‒Schmidt reaction to the target compounds. The E configuration of 19-[3-(pyridin-3-yl)-prop-2-en-1-one]-fragment was established by X-ray analysis. Screening of cytotoxic activity against NCI-60 cancer cell line panel revealed, that messagenin derivative 9 has the highest activity with GI50 value ranged from 0.304 to 0.804 µM. A colorimetric SRB assay revealed for the 2,30-bis-furfurylidene derivative 11 and 30-bromo-20-oxo-29-nor-3,28-diacetoxy-betulin 16 cytotoxic activity against breast carcinoma MCF-7 and ovarian carcinoma A2780 cell lines. Compounds 11 and 13 acted also as inhibitors of the enzyme α-glucosidase (from S. saccharomyces) with IC50 values of 1.76 µM and 3.3 µM thus being 97- and 52-fold more active than standard acarbose. Antiviral potency of compounds 12 and 14 against HCMV, HSV-1 and HPV is also discussed.[Formula: see text].