Anti-hyperglycemic and genotoxic studies of 1-O-methyl chrysophanol, a new anthraquinone isolated from Amycolatopsis thermoflava strain SFMA-103.

The compound 1-O-methyl chrysophanol (OMC) which belongs to a class of hydroxyanthraquinones was isolated from Amycolatopsis thermoflava strain SFMA-103 and studied for their anti-diabetic properties. OMC was evaluated as an anti-diabetic agent based on in silico studies which initially predicted the binding energy with α-amylase (-188.81 KJ mol-1) and with α-glucosidase (70.53 KJ mol-1). Further, these results were validated based on enzyme inhibition assays where OMC demonstrated enzyme inhibitory activity towards α-amylase (IC50 3.4 mg mL-1) and α-glucosidase (IC50 38.49 µg mL-1). To confirm the anti-diabetic activity, in vivo studies (oral dose in Wistar rats) revealed that OMC inhibited significantly the increase in glucose concentration at 100 mg/kg as compared to starch control (p < 0.05). Further, to understand the safety of OMC as a therapeutic agent, the genotoxic analysis was performed in both in vitro Chinese Hamster Ovary cells (250, 500, and 1000 µM/mL) and in vivo Swiss albino mice (250, 500, and 1000 mg/kg). In vitro results showed that OMC concentration of up to 250 µM/mL did not elicit significant changes in CAs, MI, and MN counts in CHO cells. Similarly, in mice experiments (i.p. injection), no significant changes in CAs, MI, and MN induction were observed till 500 mg/kg of OMC when compared with chrysophanic acid (Cy) (200 mg/kg). In addition, mice that received the lowest dose of OMC (250 mg/kg) did not show any histological changes in liver, kidney, and heart. The study concluded that five times higher therapeutic dose (100 mg/kg) of OMC can be utilized against hyperglycemia with no genotoxic effects.

Synthesis and biological evaluation of novel benzyl-substituted flavones as free radical (DPPH) scavengers and α-glucosidase inhibitors.

Pharmacologically motivated natural product investigations have yielded a large variety of structurally unique lead compounds with interesting biomedical properties, but the natural roles of these molecules often remain unknown. In the present investigation, a series of benzyl substituted-flavone derivatives have been synthesized from the lead compounds and were screened against 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and α-glucosidase inhibitory properties. The resulting activity profiles of these flavone derivatives were compared for degree of similarity to the profile of 1-3. Most of the synthesized derivatives displayed potent activities when compared to the parent compounds. Maximum potencies for DPPH free radical scavenging activity were observed only in compounds containing the 4-hydroxyl substitution and 3-methoxyl group on the phenyl ring. While the 2- and 4-hydroxyl group substitutions on the phenyl ring seem to be crucial for the intestinal α-glucosidase inhibitory activity.

alpha-Glucosidase inhibitory antihyperglycemic activity of substituted chromenone derivatives.

Series of 3,4- and 3,6-disubstituted chromenones including new chromenone derivatives were synthesized applying various synthetic strategies including Pechmann condensation, Knoevenagel condensation, Reimer-Tiemann reaction and Suzuki coupling in very good yields. Synthesized compounds (4a-z) were screened for in vitro alpha-glucosidase inhibitory and 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activities. Majority of compounds displayed varying degrees of alpha-glucosidase inhibitory and DPPH scavenging activity. Compound 4x emerged as the most potent alpha-glucosidase inhibitor in present series of compounds owing to the presence of 3-acetyl-6-(6-methoxy-3-pyridyl) group on chromenone; however, it could not display DPPH scavenging activity and was found to be mixed non-competitive type inhibitor of rat intestinal alpha-glucosidase. When tested in vivo for antihyperglycemic activity in starch loaded Wistar rats, it displayed significant antihyperglycemic property. This is the first report assigning rat intestinal alpha-glucosidase inhibitory property for this class of new chromenones and presents new family of compounds possessing alpha-glucosidase inhibitory activities and antihyperglycemic property. Compound 4x may serve as an interesting new compound for the development of therapeutics targeted against diet-induced hyperglycemia in diabetes.

An unusual novel anti-oxidant dibenzoyl glycoside from Salvinia natans.

An unusual novel and significant anti-oxidant 1,2-dibenzoyl glycoside, natansnin (1), has been isolated from Salvinia natans. The structure of 1 was established by the study of NMR and CD spectral data.

Dolichandroside A, a new alpha-glucosidase inhibitor and DPPH free-radical scavenger from Dolichandrone falcata seem.

A new phenylpropanoid glycoside, dolichandroside-A, together with seven known compounds alpha-lapachone, lapachol, aloesaponarin II, 8-hydroxydehydroiso-alpha-lapachone, beta-sitosterol, 3,8-dihydroxydehydroiso-alpha-lapachone and verbascoside were isolated from the active ethyl acetate soluble extract of heartwood of Dolichandrone falcata. All except for dolichandroside-A are known compounds, but have been isolated for the first time from this plant. The structure of all these compounds was determined on the basis of 1D- and 2D-NMR spectral data. All the isolates were tested for alpha-glucosidase inhibitory and DPPH radical scavenging activity. This is the first report identifying DPPH scavenging activity and alpha-glucosidase inhibitory activity in D. falcata. Furthermore, along with a new compound, dolichandroside-A, this study also assigns for the first time alpha-glucosidase inhibitory activity to verbascoside and aloe saponarin-II.

Inhibition of alpha-glucosidase and amylase by bartogenic acid isolated from Barringtonia racemosa Roxb. seeds.

Barringtonia racemosa presents a wide range of therapeutic applications. In the course of identifying bioactives from Indian medicinal plants it was observed that the hexane, ethanol and methanol extracts of B. racemosa seeds displayed potent yeast and intestinal alpha-glucosidase inhibitory activities. The methanol extract was found to be superior among them. However, none of the extracts exhibited pancreatic alpha-amylase inhibitory activity, rather the ethanol and methanol extracts accelerated the alpha-amylase enzyme activity. Interestingly, however, bartogenic acid isolated from the methanol extract inhibited alpha-amylase also. This is the first report identifying alpha-glucosidase inhibitory activity in B. racemosa seed extracts and assigning to bartogenic acid an alpha-glucosidase and amylase inhibitory property. The presence of bartogenic acid in B. racemosa seeds as a major compound is also reported for the first time in this communication.

Free-radical-scavenging and xanthine oxidase inhibitory constituents from Stereospermum personatum.

Bioassay-guided fractionation of different extracts of both stem and stem bark of Stereospermum personatum led to the isolation of free-radical-scavenging and xanthine oxidase inhibitory molecules along with three new anthraquinones, sterequinones F-H (1-3), a new naphthoquinone, sterequinone I (4), two new phenethyl esters, 2(4'-hydroxyphenyl)ethyl undecanoate (14) and 2(4'-hydroxyphenyl)ethyl nonacosanoate (15), and a new 3,4,5-trimethoxycinnamyl ether, 2-methoxy-4-[3'-(3'',4'',5''trimethoxyphenyl)allyloxymethyl]phenol (16), together with known compounds. The antioxidant and xanthine oxidase inhibitory potentials of the isolated compounds are reported.