Nisar Ullah

New potent inhibitors of tyrosinase: Novel clues to binding of 1,3,4-thiadiazole-2(3H)-thiones, 1,3,4-oxadiazole-2(3H)-thiones, 4-amino-1,2,4-triazole-5(4H)-thiones, and substituted hydrazides to the dicopper active site

A series of 1,3,4-thiadiazole-2(3H)-thiones, 1,3,4-oxadiazole-2(3H)-thiones, 4-amino-1,2,4-triazole-5(4H)-thiones, and substituted hydrazides were tailored and synthesized as new potent inhibitors of tyrosinase. The rationale for inhibitor design was based on the active site structural evidence from the crystal structures of bacterial tyrosinase and potato catechol oxidase enzymes. Kinetic and active site binding studies suggested mono-dentate binding of thiadiazole, oxadiazole, and triazole rings to the active site dicopper center of tyrosinase including hydrophobicity contributing to the potent inhibition. Kinetic plots showed mixed-type of inhibition by all 25 compounds. Substitutions at C3 of the triazole ring and C5 of the thiadiazole/oxadiazole rings were found to be playing a major role in the high binding affinity to tyrosinase. The current work may help develop new potent tyrosinase inhibitors against hyperpigmentation including potential insecticides.

Withanolides from Physalis peruviana

Two new withanolides isolated from the whole plant material of Physalis peruviana (Solanaceae) have been characterized as (20R,22R)-5α,6β,14α,20,27-pentahydroxy-1-oxowith-24-enolide, and (20S,22R)-5β,6β-epoxy-4β,14β,15α-trihydroxy-1-oxowith-2,24-dienolide in addition to the known withanolides, withaphysanolide and viscosalactone B on the basis of spectroscopic techniques and chemical transformations.

Enantioselective [4 + 2]-Annulation of Oxadienes and Allenones Catalyzed by an Amino Acid Derived Phosphine: Synthesis of Functionalized Dihydropyrans.

An enantioselective [4 + 2]-annulation process between cyano-activated oxadienes and allenones is developed. An l-valine-derived phosphine was efficient in catalyzing the reaction, and a wide range of highly functionalized dihydropyrans were prepared in high yields and with excellent enantioselectivities.

Coumarinolignoid glycoside from Daphne oleoides

Abstract A new coumarinolignoid glycoside, daphneticin-4″-O-a- d -glucopyranoside, alongwith the known, daphneticin, have been isolated from the whole plant extract of Daphne oleoides. The structures of these compounds were elucidated on the basis of chemical and spectroscopicevidence.

Organocatalyzed solvent free an efficient novel synthesis of 2,4,5-trisubstituted imidazoles for α-glucosidase inhibition to treat diabetes.

A new and efficient solvent free synthesis of 2,4,5-trisubstituted imidazoles (3a-3j) was achieved by N-acetyl glycine (NAG) catalyzed three components condensation of aldehydes, benzil and ammonium acetate. Our synthetic methodology accommodated a range of various substituted alkyl and aryl aldehydes. Evaluation of α-glucosidase inhibitory activity of these imidazole derivatives revealed that most of them presented good α-glucosidase inhibition at low micro-molar concentrations. Among the synthesized compounds, compound 3c, bearing the ortho-hydroxy phenyl substituent at position 2 displayed the highest inhibitory activity with an IC50 value 74.32±0.59 μM. In silico molecular docking for all compounds and computational studies of the most active compound 3c were also performed.

Chemical constituents of Daphne oleoides

Abstract The isolation of daphnetin 8-O-β- d -glucopyranoside (1), 4-ethoxybenzoic acid, 4-hydroxybenzoic acid and grantioidin from Daphne oleides (whole plant) is reported along with 1H- and 13C-NMR spectra of 1.

A dicoumarin glycoside from Daphne oleoides

Abstract From the whole plant extract of Daphne oleoides, a new dicoumarin glycosidegulsamanin, has been isolated. Its structure was established as 6,7-dihydroxy-3-methoxy-8-[2-oxo-2H-1-benzopyran-7- (O-β- d -glucopyranosyl)-8-yl]-2H-1-benzopyran-2-one, on the basisof extensive NMR spectral studies, as well as by chemical methods.

A lignan from Daphne oleoides

Abstract A new lignan has been isolated from the whole plant extract of Daphne oleoides besides the known taxiresinol and lariciresinol. The structure of the new lignan was established as 4,9′-dihydroxy-3′,4′,5-trimethoxy-7′,9-epoxylignan by spectroscopic methods.

Enantioselective Phosphine-Catalyzed Formal [4+4] Annulation of α,β-Unsaturated Imines and Allene Ketones: Construction of Eight-Membered Rings

The first highly enantioselective phosphine-catalyzed formal [4+4] annulation has been developed. In the presence of amino-acid-derived phosphines, the unprecedented [4+4] annulations between benzofuran/indole-derived α,β-unsaturated imines and allene ketones proceeded smoothly, thus affording azocines, bearing either a benzofuran or an indole moiety, in excellent yields and with nearly perfect enantioselectivities (≥98 % ee in most cases). This work marks the first efficient asymmetric construction of optically enriched eight-membered rings by phosphine catalysis.

Design and Synthesis of New Dual Binding Site Cholinesterase Inhibitors: in vitro Inhibition Studies with in silico Docking

Cholinesterases (ChEs) play a vital role in the regulation of cholinergic transmission. The inhibition of ChEs is considered to be involved in increasing acetylcholine level in the brain and thus has been implicated in the treatment of Alzheimer’s disease. We have designed and synthesized a series of novel indole derivatives and screened them for inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Most of the tested compounds exhibited inhibitory activity against AChE and BChE. Among them 4f and 6e showed the highest AChE inhibitory activity with IC50 91.21±0.06 and 68.52±0.04 μM, respectively. However compound 5a exhibited the highest inhibitory activity against BChE (IC50 55.21±0.12 μM).