Α-glucosidase Inhibition Studies Research Articles

Chiral (S)-BINOL-phosphates: Design, synthesis and their antibacterial and α-glucosidase inhibition studies

A new series of chiral (S)-BINOL-derived phosphoric acid derivatives (8a-k) with 3,3′-disubstitution were successfully synthesized under microwave irradiation, yielding high product quantities within a short reaction time. The antibacterial and α-glucosidase inhibitory properties of these compounds were evaluated. Notably, compound 8b exhibited remarkable antibacterial efficacy against B. subtilis, S. aureus, S. epidermidis, P. aeruginosa, and K. pneumoniae, with a MIC value of 1.17 g mL−1. Furthermore, the electron-withdrawing nitro group-containing derivative, 8d displayed potent antibacterial activity (MIC = 1.17 g mL−1) against B. subtilis, S. epidermidis, and E. coli. Among the synthesized compounds, compound 8b, containing chloro substitutions at the 3,5-positions of the phenyl groups in (S)-3,3′-disubstituted BINOL, demonstrated the most noteworthy α-glucosidase inhibitory activity with IC50 value of 2.067 ± 0.017 M.

In vitro α-amylase and α-glucosidase inhibition study of dihydropyrimidinones synthesized via one-pot Biginelli reaction in the presence of a green catalyst

A green catalyst WELPSA-catalyzed three-component condensation (Biginelli) process involving an aldehyde, barbituric/thiobarbituric/1,3-dimethylbarbituric acid, and urea/thiourea/guanidine hydrochloride in a single pot in presence of a green solvent for the production of DHPM have been presented. The catalyst is reusable and this methodology is scalable. By using the in vitro experiments, the antidiabetic potentiality of synthesized compounds that inhibit α-amylase along with α-glucosidase efficiencies was assessed. All the synthesized compounds except for 4a and 4e, showed the most significant inhibition for α-amylase and α-glucosidase activities. Among the synthesized DHPM compounds, 4c and 4b exhibited significant inhibition profiles compared to the standard antidiabetic drug acarbose. Furthermore, synthesized substances' energy-minimized structures, 3D structures, and DFT calculations were performed using Gaussian 09 software, hybrid models, and MM2 force approaches. Strong hydrogen bonds with amino acid residues Arg-672, Arg-600, Trp-613, Asp-404, Asp-282, and Asp-616 indicate that an α-glucosidase-inhibitory peptide may have hypoglycemic efficacy confirmed by the molecular docking study of the synthesized DHPM.

Anti-diabetes and anti-breast cancer of bioactive compounds-enriched fractions isolated from hemp (Cannabis sativa L. subsp.)

Diabetes and breast cancer are connected via the presence of hyperinsulinemia, inflammation caused by obesity, and changes in sex hormones. The present study investigated the ability of enriched fractions isolated from hemp (Cannabis sativa L. subsp.) to inhibit α-glucosidase and exhibit cytotoxic effects on Michigan Cancer Foundation-7 (MCF-7) and MD Anderson-metastatic breast-231 (MDA-MB-231) cells. The enriched fractions were found to include tetrahydrocannabinol, cannabidiol, phenolics, flavonoids, terpenoids, and alkaloids. The phytochemical compositions of the extracts were evaluated for their correlation with α-glucosidase inhibitory activities and their effects on MCF-7 and MDA-MB-231 cells. In the α-glucosidase inhibition studies, the α-glucosidase inhibitory activities (maltase and sucrase) of CL3 exhibited a greater inhibitory impact when compared with acarbose, with IC50 values of 3.36 ± 0.90 and 2.15 ± 0.17 mg/ml, respectively, with statistical significance (p < 0.05). The corresponding IC50 values were 2.15 ± 0.17 and 0.40 ± 0.09 mg/ml. According to a kinetic examination, intestinal maltase and sucrase were inhibited by CL3 in uncompetitive and noncompetitive manners. Cell viability assays after 24 hours of treatment of the cancer cells with enriched fractions using MTT were observed. Cancer cell proliferation was effectively inhibited by the enriched fraction at concentrations of 100–200 ppm, with statistical significance at the confidence level of p < 0.05. In addition, the results show that the high doses of CR5, CR6, CS7, and CS8 induced apoptosis. Our findings indicate that hemp has both anti-diabetic and anti-cancer capabilities, which might pave the way for future advancements in drug research.

Synthesis, characterization, DNA interaction, molecular docking, and α-amylase and α-glucosidase inhibition studies of a water soluble Zn(II) phthalocyanine.

In this study, 2(3),9(10),16(17),23(24)-tetrakis-[(N-methyl-(1-benzylpiperidin-4-yl)oxy)phthalocyaninato]zinc(II) iodide (ZnPc-2) was synthesized and characterized using spectral methods (FT-IR, 1H-NMR, UV-Vis and mass spectroscopy). The interaction of ZnPc-2 with DNA was investigated by using the UV/Vis titrimetric method, thermal denaturation profile, agarose gel electrophoresis and molecular docking studies. Additionally, the antidiabetic activity of ZnPc-2 was revealed spectroscopically by studying α-amylase and α-glucosidase inhibition activities. The spectroscopic results indicated that ZnPc-2 effectively binds to calf thymus-DNA (CT-DNA) with a Kb value of 7.5 × 104 M-1 and interacts with CT-DNA via noncovalent binding mode. Gel electrophoresis results also show that ZnPc-2 binds strongly to DNA molecules and exhibits effective nuclease activity even at low concentrations. Furthermore, docking studies suggest that ZnPc-2 exhibits a stronger binding tendency with DNA than the control compounds ethidium bromide and cisplatin. Consequently, due to its strong DNA binding and nuclease activity, ZnPc-2 may be suitable for antimicrobial and anticancer applications after further toxicological tests. Additionally, antidiabetic studies showed that ZnPc-2 had both α-amylase and α-glucosidase inhibition activity. Moreover, the α-glucosidase inhibitory effect of ZnPc-2 was approximately 3500 times higher than that of the standard inhibitor, acarbose. Considering these results, it can be said that ZnPc-2 is a moderate α-amylase and a highly effective α-glucosidase inhibitor. This suggests that ZnPc-2 may have the potential to be used as a therapeutic agent for the treatment of type 2 diabetes.

Design, synthesis and α-glucosidase inhibition study of novel pyridazin-based derivatives

Design, synthesis and α-glucosidase inhibition study of novel pyridazin-based derivatives

Novel copper complexes of metronidazole and metronidazole benzoate: synthesis, characterization, biological and computational studies

Synthesis and characterization of novel copper complexes of metronidazole benzoate (MTZ Benz), metronidazole (MTZ) in the presence of another ligand; dichloroacetic acid (DCA) were compared and reported in the present work. Different bacterial and fungus strains were ascertained to evaluate the biological potency of the synthesized complexes, that is, Escherichia coli, Bordetella bronceptica, Staphylococcus epidermidis, Baccilus pumilus, Staphylococcus aureus and yeast strain Saccharomyces cerevisiae. Agar diffusion method was employed to investigate in vitro antibacterial activities of the synthesized metal complexes and the tested parent ligands. α-Amylase and α-glucosidase inhibition studies of the synthesized complexes were also carried out. The antibacterial potential and α-amylase and α-glucosidase inhibition studies of complexes were further investigated by molecular docking studies, which supported the experimental results. Significant α-amylase and α-glucosidase inhibition activities were shown by the synthesized complexes. S-1 and S-5 were found to be most inhibitors of α-amylase and α-glucosidase having IC50 42.50, 44.80 and 4.52 µg/mL, 4.80 µg/mL, respectively. The newly synthesized copper complexes showed overall better biological activities compared to each parent ligands used. Communicated by Ramaswamy H. Sarma

English

In this study, we investigated the promising potential of Anadenanthera colubrina bark extract (BEAc) as a product to combat diabetes mellitus (DM). We evaluated the inhibitory effects of BEAc on α-glucosidase and the oxidation of biomolecules, as well as its main phytoconstituents. In terms of free radical scavenging, BEAc exhibited a dose-effect relationship. BEAc was more efficient than rutin and butylated hydroxytoluene and similar to ascorbic acid at the same concentrations. Evaluation of the IC50 confirmed the good activity of BEAc compared to positive controls and statistically determined to be equal to ascorbic acid. In in vitro α-glucosidase inhibition studies, BEAc generated 31 times more potent inhibition than acarbose and was dose-dependent at the concentrations tested. Lineweaver-Burk and Michaelis-Menten plots obtained for kinetic analysis showed that BEAc competitively inhibited the α-glucosidase catalyzed reaction. Chemical analysis of BEAc by HPLC revealed that the plant is rich in phenolic compounds and confirmed its capacity to inhibit α-glucosidase. Fourteen compounds were identified by reference to authentic standards: Gallic acid, catechin, syringic acid, chlorogenic acid, p-coumaric acid, naringin, vitexin, rutin, isorhamnetin, hesperidin, myricetin, morin, rosmarinic acid, and quercetin. Thus, this study provides the first evidence of the antidiabetic activity of A. colubrina bark and determines its possible modes of action on carbohydrate metabolism via inhibition of α-glucosidase and the control of biomolecule oxidation. These data support the potential use of this plant for the development of promising multi-target therapy products combining postprandial hyperglycemia control and biomolecule oxidation control. Key words: Kinetic analysis, phenolic content, diabetes mellitus, oxidation of biomolecules.

Synthesis, molecular docking, α-glucosidase inhibition, and antioxidant activity studies of novel benzimidazole derivatives

A novel series of N-methyl/benzyl-substituted benzimidazolyl-linked para-substituted benzyl-based compounds containing 2,4-thiazolidinediones, dimethyl malonate (DMM), and diethyl malonate (DEM) 17–27 were designed, docked, synthesized, and evaluated for their antidiabetic activity studies. Structures of all the synthesized compounds were confirmed through 1H NMR, 13C NMR, FTIR, and mass spectrometry. Four targeted compounds (17–18 and 22–23) showed good inhibitory potential in the range of 4.10 ± 0.01 to 9.12 ± 0.06 µM. Furthermore, synthesized compounds 17–27 were evaluated for their antioxidant potential and compared with standard ascorbic acid and results showed that compound 18 (EC50 = 0.176 ± 0.002 mM) being the most active. Compounds 17–18 and 22–23 exhibited prominent antidiabetic as well as antioxidant activity. Compound 18 was considered a promising candidate for this series. The designed molecules were docked into α-glucosidase protein (PDB Code. 3TOP) to develop a correlation with the α-glucosidase inhibition studies and were also additionally docked into PPARγ proteins (PDB ID: 2PRG) with rosiglitazone (standard drug) to study their PPARγ binding affinity in comparison with rosiglitazone and to classify these compounds for their PPARγ agonistic behavior.

Synthesis, characterization, α-glucosidase inhibition and molecular modeling studies of some pyrazoline-1H-1,2,3-triazole hybrids

A series of molecular hybrids based on pyrazoline and 1,2,3-triazole pharmacophores were designed and synthesized as antidiabetic agents. The structures of all the derivatives were confirmed using 1H NMR, 13C NMR and HRMS. Moreover, the structure of one of the intermediate precursor was confirmed using single crystal X-ray diffraction. The anti-diabetic potential of all the synthesized compounds was explored in terms of α-glucosidase inhibition studies. All the compounds exhibited remarkable inhibition of α-glucosidase. The inhibition of enzyme by compound TPZ2 (IC50 = 41.29 ± 0.123) and TPZ8 (IC50 = 47.94 ± 0.246) was found to be more promising as compared to the reference drug i.e., Acarbose (IC50 = 60.68 ± 0.123). The inhibition of α-glucosidase was further supported by in silico docking studies. In order to explore the most favorable binding interactions the binding pose of lowest energy was then subjected to molecular dynamics studies. Both the ligands have reasonable interactions with the protein active site with average interaction energy of −270.88 kcal/mol and −273.90 kcal/mol for TPZ8 and TPZ2, respectively.

Dioxidovanadium(V) complexes of a tridentate ONO Schiff base ligand: Structural characterization, quantum chemical calculations and in-vitro antidiabetic activity

Two new dioxidovanadium(V) complexes [V(O)2(L)]Him 1 and [V(O)2(L)]H2Meim 2, incorporating tridentate ligand Nicotinic acid (2-hydroxy-3-methoxy-benzylidene)-hydrazide (H2L) and imidazoles (Him = imidazole and H2Meim = methylimidazole) was substantiated. The crystal structures of both complexes were solved by single-crystal X-ray analysis. In both complexes, the V(V) center is coordinated by ONO donar set of L2- ligand and two oxido groups in a distorted square pyramidal geometry. UV–visible spectra, infrared spectra and electrochemical properties of both complexes were also reported. Room temperature magnetic susceptibility was performed to disclose the diamagnetic nature of complexes 1 and 2. The quantum chemical calculations authenticated the molecular structures and reactivity of the complexes. Antidiabetic activities of the complexes have also been investigated. An antidiabetic feature like α-amylase and α-glucosidase inhibition studies made them promising agents as inhibitors of insulin enzyme.

Design, synthesis and α-glucosidase inhibition study of novel embelin derivatives

Embelin is a naturally occurring para-benzoquinone isolated from Embelia ribes (Burm. f.) of the Myrsinaceae family. It was first discovered to have potent inhibitory activity (IC50 = 4.2 μM) against α-glucosidase in this study. Then, four series of novel embelin derivatives were designed, prepared and evaluated in α-glucosidase inhibition assays. The results show that most of the embelin derivatives synthesised are effective α-glucosidase inhibitors, with IC50 values at the micromolar level, especially 10d, 12d, and 15d, the IC50 values of which are 1.8, 3.3, and 3.6 μM, respectively. Structure–activity relationship (SAR) studies suggest that hydroxyl groups in the 2/5-position of para-benzoquinone are very important, and long-chain substituents in the 3-position are highly preferred. Moreover, the inhibition mechanism and kinetics studies reveal that all of 10d, 12d, 15d, and embelin are reversible and mixed-type inhibitors. Furthermore, docking experiments were carried out to study the interactions between 10d and 15d with α-glucosidase.

α-Glucosidase Inhibition and Molecular Docking Studies of Natural Brominated Metabolites from Marine Macro Brown Alga Dictyopteris hoytii.

Bioassay guided isolation of the methanolic extract of marine macro brown alga Dictyopteris hoytii afforded one new metabolite (ethyl methyl 2-bromobenzene 1,4-dioate, 1), one new natural metabolite (diethyl-2-bromobenzene 1,4-dioate, 2) along with six known metabolites (3–8) reported for the first time from this source. The structure elucidation of all these compounds was achieved by extensive spectroscopic techniques including 1D (1H and 13C) and 2D (NOESY, COSY, HMBC and HSQC) NMR and mass spectrometry and comparison of the spectral data of known compounds with those reported in literature. The in vitro α-glucosidase inhibition studies confirmed compound 7 to be the most active against α-glucosidase enzyme with IC50 value of 30.5 ± 0.41 μM. Compounds 2 and 3 demonstrated good inhibition with IC50 values of 234.2 ± 4.18 and 289.4 ± 4.91 μM, respectively, while compounds 1, 5, and 6 showed moderate to low inhibition. Furthermore, the molecular docking studies of the active compounds were performed to examine their mode of inhibition in the binding site of the α-glucosidase enzyme.

In vitro alpha-glucosidase inhibitory, total phenolic composition, antiradical and antioxidant potential of Heteromorpha arborescens (Spreng.) Cham. & Schltdl. leaf and bark extracts

Heteromorpha arborescens (syn. H. trifoliata) leaves and bark are used in traditional medicine by many ethnic groups in central and southern Africa against diabetes, headache, pain and fever. The aim of this study was to evaluate the in vitro α-glucosidase inhibition, free radical scavenging and antioxidant potentials of hexane, ethyl acetate and methanol extracts of H. arborescens leaves and bark. In in vitro α-glucosidase inhibition study, the ethyl acetate extract of leaves (EAL) and methanol extracts of bark (MB) had good effects compared to other extracts. EAL and MB extracts showed 50% α-glucosidase inhibition at a concentration of 3.12 ± 0.62 and 3.10 ± 1.73 mg/ml, respectively. The free radical scavenging and antioxidant potentials of H. arborescens leaf and bark extracts were evaluated using the ferric-reducing antioxidant power assay (FRAP), 2,2-diphenyl-1-picryl hydrazyl (DPPH), hydroxyl, hydrogen peroxide, superoxide radical scavenging assays and β-carotene/linoleic acid assay. The EAL and MB extracts showed strong free radical scavenging and antioxidant activities compared to other extracts. These results indicate that H. arborescens leaves and bark have significant potential to be used as a natural α-glucosidase inhibitor with free radical scavenging and antioxidant properties.

Bioactivity guided isolation of antidiabetic and antioxidant compound from Xylocarpus granatum J. Koenig bark

The present study was designed to identify antidiabetic and antioxidant constituents from ethanol bark extract of a medicinally important mangrove plant Xylocarpus granatum J. Koenig, using in vitro bioactivity-guided fractionation. The repeated fractionation of X. granatum ethanol bark extract (XGEB) by silica gel column chromatography yielded a compound with strong antidiabetic and antioxidant potential. The bioactive compounds likely to be present in the XGEB fraction were identified by FT-IR, 1H & 13C NMR and MS analysis and determined as a limonoid derivative Xyloccensin-I, by comparing spectral data with the literature reports. The isolated compound demonstrated excellent in vitro antidiabetic potential IC50 values of 0.25 and 0.16mg/ml, respectively for α-amylase and α-glucosidase inhibition study. The antioxidant potential assayed by DPPH, ABTS, superoxide and hydrogen peroxide scavenging studies exhibited that the isolated compound could scavenge these free radicals with IC50 values of 0.041, 0.039, 0.096 and 0.235mg/ml, respectively. Further, in silico study was performed to find the antidiabetic activity of Xyloccensin-I by docking it against α-glucosidase enzyme. The study demonstrated that Xyloccensin-I have satisfactory interactions and binding energies when docked into target which further confirms the possible mode of antidiabetic action of the isolated compound. The bioactivity assays further asserts the antidiabetic and antioxidant efficacy of the isolated compound which strongly suggests that Xyloccensin-I holds promise in the pharmaceutical industry. The results from this study provide new mechanistic evidence justifying, at least in part, the traditional use of X. granatum extract for antidiabetic and antioxidants activities.

Model investigations for vanadium-protein interactions: Synthesis, characterization and antidiabetic properties

Reaction of NNO donor Schiff bases with vanadyl sulphate afforded the complexes viz., [VO(L1)(H2O)]NO31, [VO(L2)(H2O)]NO32, [VO(L2)(ImH)2]SO4·H2O 3 and [VO(L1)ImH]NO34 (where, L1 = Acetic acid (2-hydroxy-3-methoxy-benzylidene)-hydrazide and L2 = 5-bromo-2-[(E)-(pyridine-2-ylhydrazono)methyl]phenol). In complex 3 the oxidation state of vanadium was found to be +5, while in rest all complexes it was +4. The crystal structure of complex 3 was solved by single crystal X-ray analysis. In addition to synthesis, optical, infrared and electrochemical properties of these complexes were also carried out. Electron paramagnetic spectra of oxidovanadium(IV/V) complexes is reported as well. Docking experiments were performed to study the molecular binding behaviour of all complexes with α-glucosidase enzyme. An antidiabetic feature like α-amylase and α-glucosidase inhibition studies made them promising candidates as inhibitors of insulin enzyme.

Three novel Cu(II), Cd(II) and Cr(III) complexes of 6−Methylpyridine−2−carboxylic acid with thiocyanate: Synthesis, crystal structures, DFT calculations, molecular docking and α-Glucosidase inhibition studies

Novel complexes of 6−methylpyridine−2−carboxylic acid and thiocyanate {[Cu(NCS)(6-mpa)2], (1); [Cd(NCS)(6-mpa)]n, (2); [Cr(NCS)(6-mpa)2·H2O], (3)} were synthesized, and their structures were characterized by XRD analysis, FT–IR and UV–Vis spectroscopic techniques. The inhibitory activities of the synthesized complexes (1–3) on α-glucosidase were determined by using genistein reference compound. Furthermore, the optimized geometry and vibrational harmonic frequencies for the complexes 1–3 were obtained by DFT/HSEh1PBE/6–311G(d,p)/LanL2DZ level. Electronic spectral properties were examined by using TD-DFT/HSEh1PBE/6–311G(d,p)/LanL2DZ level with CPCM model. Additionally, major contributions to the electronic transitions were determined via Swizard program. The refractive index, linear optical and non−nonlinear optical parameters of the complexes 1–3 were investigated at HSEh1PBE/6–311G(d,p) level. The docking studies of the complexes 1–3 to the binding site of the target protein (the template structure S. cerevisiae isomaltase are fulfilled. Lastly, natural bond orbital analysis was used to investigate inter- and intra-molecular bonding and interaction among bonds.

EVALUATION OF α-GLUCOSIDASE INHIBITORY POTENTIAL OF METHANOLIC LEAF EXTRACT OF OCIMUM CANUM

Objective: The present investigation was designed to study the inhibitory effects of methanolic leaf extract of Ocimum canum (O. canum) on α-glucosidase using in vitro model followed by an assessment of bioactive compounds.Methods: The methanolic leaf extract was prepared by Soxhlet extraction method and partially purified by thin layer chromatography (TLC). Each band was subjected to α-glucosidase inhibition study. The positive bands were further characterized by high-performance liquid chromatography (HPLC) and quadrupole time of flight (Q-TOF) micro mass spectrometer.Results: Out of the several combinations of solvent systems, toluene, ethyl acetate and formic acid combination in the ratio of 7:2:1 revealed 5 bands on the TLC sheet. Among all the TLC bands, 2 bands (band A and B) showed the significant inhibitory effect on α-glucosidase activity. HPLC analysis of band A and B revealed the presence of two important polyphenolic compounds, namely rosmarinic acid (RA) and ursolic acid (UA). Q-TOF micromass spectrometer analysis revealed the percentage availability of RA, caffeic acid, tartaric acid, quercetin and other polyphenolic components in the bioactive bands.Conclusion: The study revealed that methanolic leaf extract of O. canum exhibits potent inhibition of α-glucosidase activity. Inhibition of α-glucosidase activity might be attributed to the presence of the polyphenolic compounds like RA and UA. Therefore, this finding can lead to the development of natural α-glucosidase inhibitors by the O. canum leaf extract.

Evaluation of In Vitro Antidiabetic and Antioxidant Activities and Preliminary Phytochemical Screening of Leaf Extracts of Avicennia officinalis

Avicennia officinalis is a medicinal mangrove plant and used in traditional folk medicine for treatment of various ailments. In the present study, the antidiabetic and antioxidant activities of petroleum ether and aqueous extracts of leaves of A. officinalis were evaluated. The antidiabetic activity was evaluated out by α-amylase and α-glucosidase inhibition study and antioxidant capacity by DPPH, superoxide and hydrogen peroxide scavenging activity of leaf extracts at various concentrations. The maximum antidiabetic activity was observed in 1.0 mg/ml of leaves extract of aqueous extracts. The maximum superoxide and hydrogen peroxide scavenging activity were exhibited by aqueous extracts with IC50 values of 0.27 and 0.17 mg/ml respectively and maximum DPPH scavenging activity was shown by petroleum ether extracts with IC50 value of 0.25 mg/ml. The qualitative and quantitative phytochemical analysis also showed presence of different phytochemicals including phenols, flavonoids and tannins which may be attributed to their antidiabetic and antioxidant activities. Thus, the present study gives a clear evidence that leaf extracts of A. officinalis possess both antidiabetic and antioxidant activities.

Antidiabetic components of Cassia alata leaves: Identification through α-glucosidase inhibition studies

Context: Cassia alata Linn. [syn. Senna alata (L.) Roxb.] (Caesalpiniaceae) is used for treating various disease conditions including diabetes but its mechanism(s) of action and active principles remain to be elucidated.Objective: The antidiabetic principles were identified using an in vitro α-glucosidase inhibition study.Materials and methods: The methanol extract of leaves of C. alata, which showed potent α-glucosidase inhibitory activity (IC50, 63.75 ± 12.81 µg/ml), was fractionated. Active fractions were taken for further analysis by a variety of techniques including HPLC and Combiflash chromatography. The identity of the isolated compounds was established by spectroscopic analysis while their potential antidiabetic activity was assessed by in vitro enzyme inhibition studies.Results: The α-glucosidase inhibitory effect of the crude extract was far better than the standard clinically used drug, acarbose (IC50, 107.31 ± 12.31 µg/ml). A subsequent fractionation of the crude extract was made using solvents of ascending polarity (petroleum ether, chloroform, ethyl acetate, n-butanol and water). The ethyl acetate (IC50, 2.95 ± 0.47 µg/ml) and n-butanol (IC50, 25.80 ± 2.01 µg/ml) fractions which contained predominantly kaempferol (56.7 ± 7.7 µM) and kaempferol 3-O-gentiobioside (50.0 ± 8.5 µM), respectively, displayed the highest carbohydrate enzyme inhibitory effect.Discussion: One of the possible antidiabetic mechanisms of action of C. alata is by inhibiting carbohydrate digestion. This is the first report on α-glucosidase activity of kaempferol 3-O-gentiobioside.Conclusion: Considering the activity profile of the crude extract and isolated bioactive compounds, further in vivo and clinical studies on C. alata extracts and compounds are well merited.

α-Glucosidase Inhibitory Activity of Kaempferol-3-O-rutinoside

Quercetin, kaempferol and to a lesser extent rutin have been reported to have antidiabetic activities when assessed by various assay models including in vitro alpha-glucosidase inhibition studies. A related structural analogue, kaempferol-3-O-rutinoside (KR) however has not yet been studied for such biological effects. It was found that KR is a potent inhibitor of alpha-glucosidase in vitro with over 8-times more activity than the reference antidiabetic drug, acarbose. Furthermore, KR displayed a synergistic effect with a less potent flavonoid aglycones, kaempferol and quercetin. The structure-activity profile of these drugs and implications of drug combinations are discussed.