Shamsun Nahar Khan

Alpha-glucosidase and tyrosinase inhibitors from fungal hydroxylation of tibolone and hydroxytibolones

Sixteen new and one known metabolites 4-20 were obtained by incubation of tibolone (1) and hydroxytibolones (2 and 3) with various fungi. Their structures were elucidated by means of a homo and heteronuclear 2D NMR and by HREI-MS techniques. The relative stereochemistry was deduced by 2D NOESY experiment. Metabolites of tibolone (1) exhibited significant inhibitory activities against alpha-glucosidase and tyrosinase enzymes. Hydroxylations at C-6, C-10, C-11, C-15 positions and alpha,beta-unsaturation at C-1/C-2, C-4/C-5 showed potent inhibitory activities against these enzymes.

α-Glucosidase Inhibitory Activity of Triterpenoids from Cichorium intybus

Two new triterpenoids, 18alpha,19beta-20(30)-taraxasten-3beta,21alpha-diol (cichoridiol) (1) and 17-epi-methyl-6-hydroxyangolensate (intybusoloid) (2), were obtained from the methanolic extract of seeds of Cichorium intybus along with 11 known compounds, lupeol (3), friedelin (4), beta-sitosterol (5), stigmasterol (6), betulinic acid (7), betulin (8), betulinaldehyde (9), syringic acid (10), vanillic acid (11) 6,7-dihydroxycoumarin (12), and methyl-alpha-D-galactopyranoside (13). Compounds 1, 1a, and 11 showed a good alpha-glucosidase inhibitory activity.

Science at the interface of chemistry and biology: Discoveries of α-glucosidase inhibitors and antiglycation agents

Diseases are manifestations of complex biological processes in living systems. Through the applications of molecular biology and genetics, many diseases are now understood at the molecular level. This has provided researchers opportunities to develop lead molecules with the capacity of blocking a particular disease mechanism. Diabetes is a complex metabolic disorder, characterized by hyperglycemia. The first objective of antidiabetic chemotherapy is to achieve normal glycemic index. Recently, major discoveries have been made to understand how the disease progresses and manifests its complications. We have used this growing understanding to work toward discovery of effective α-glucosidase inhibitors and antiglycation agents of natural and synthetic origins. Reliable bench-top biochemical assays were employed, and several new molecular entities were studied with reference to their structure-activity relationships.

Synthesis, Spectroscopy, and Biological Properties of Vanadium(IV)–Hydrazide Complexes

The synthesis, spectroscopic, enzyme‐inhibition, and free‐radical‐scavenging properties of a series of vanadium(IV) complexes, compounds 1–10, were investigated. These complexes exhibit a dimeric structure with hydrazide ligands coordinated in a bidentate fashion. All complexes are stable in the solid state, but exhibit varying degrees of stability in solution. In coordinating solvent such as DMSO, stepwise binding of two solvent molecules at the 6th positions trans to the VO bond of the dimeric unit is observed. The dimeric compounds are converted to monomeric species in which both solvent molecules and the hydrazide ligands are coordinated to the VIV center. The free hydrazide ligands 11–20 were inactive against α‐glucosidase, but the VIV complexes showed varying degrees of inhibition, depending on the type of ligand. The DPPH‐radical‐scavenging activities of 1–20 were determined, which indicated that steric and/or electronic effects responsible for changes in geometry play important roles in terms of antioxidant potential.

Microbial transformation of oleanolic acid by Fusarium lini and α-glucosidase inhibitory activity of its transformed products

The biotransformation of a pentacyclic triterpene, oleanolic acid (1), with Fusarium lini afforded two oxidative metabolites, 2α,3β-dihydroxyolean-12-en-28-oic acid (2), and 2α,3β,11β-trihydroxyolean-12-en-28-oic acid (3). Metabolite 3 was found to be a new compound. The structures were characterized on the basis of spectroscopic studies. These metabolites exhibited a potent inhibition of α-glucosidase enzyme.

Fungal transformation of cedryl acetate and α-glucosidase inhibition assay, quantum mechanical calculations and molecular docking studies of its metabolites.

The fungal transformation of cedryl acetate (1) was investigated for the first time by using Cunninghamella elegans. The metabolites obtained include, 10β-hydroxycedryl acetate (3), 2α, 10β-dihydroxycedryl acetate (4), 2α-hydroxy-10-oxocedryl acetate (5), 3α,10β-dihydroxycedryl acetate (6), 3α,10α-dihydroxycedryl acetate (7), 10β,14α-dihydroxy cedryl acetate (8), 3β,10β-cedr-8(15)-ene-3,10-diol (9), and 3α,8β,10β -dihydroxycedrol (10). Compounds 1, 2, and 4 showed α-glucosidase inhibitory activity, whereby 1 was more potent than the standard inhibitor, acarbose, against yeast α-glucosidase. Detailed docking studies were performed on all experimentally active compounds to study the molecular interaction and binding mode in the active site of the modeled yeast α-glucosidase and human intestinal maltase glucoamylase. All active ligands were found to have greater binding affinity with the yeast α-glucosidase as compared to that of human homolog, the intestinal maltase, by an average value of approximately -1.4 kcal/mol, however, no significant difference was observed in the case of pancreatic amylase.

Microbial Hydroxylation of Hydroxyprogesterones and α-Glucosidase Inhibition Activity of Their Metabolites

Microbial transformation of 11α-hydroxyprogesterone (1) with Cunninghamella elegans, Gibberella fujikuroi, Fusarium lini, and Candida albicans yielded 11α,15α,16α-trihydroxypregn-4- ene-3,20-dione (3), 11α-hydroxy-5α-pregnane-3,20-dione (4), 6β ,11α-dihydroxypregn-4-ene-3,20- dione (5), 11α-hydroxypregna-1,4-diene-3,20-dione (6), 11α,17β -dihydroxyandrost-4-en-3-one (7), and 11α,15α-dihydroxypregn-4-ene-3,20-dione (8). On the other hand, microbial transformation of 17α-hydroxyprogesterone (2) with Cunninghamella elegans and Fusarium lini yielded 11α,17α- dihydroxypregn-4-ene-3,20-dione (9), and 17α-hydroxypregna-1,4-diene-3,20-dione (10). The structures of the metabolites 3 - 10 were deduced on the basis of spectroscopic methods. Compound 3 was identified as a new metabolite, which exhibited a promising inhibitory activity against the α-glucosidase enzyme.

A New α-Glucosidase Inhibiting Dithiadiazetidin Derivative from Symplocos racemosa

The phytochemical investigation of the n-butanol soluble fraction of Symplocos racemosa Roxb. resulted in the isolation of a new dithiadiazetidin derivative; symploate (1). Its structure was established through various 1Dand 2D NMR techniques together with high-resolution mass spectrometric techniques and spectral evidences. The symploate (1) showed moderate inhibitory activity against α-glucosidase in a concentration-dependent fashion with an IC 5 0 value of 691.1 ′ 3.29 μM.