Design, synthesis of new phenyl acetylene and isoxazole analogues of arjunolic acid as potent tyrosinase and alpha glucosidase inhibitors

The incidence of diabetes has increased globally in recent years and figures of diabetic patients were estimated to rise up to 642 million by 2040. The disorder is accompanied with various complications if not managed at the early stages, and interlinked high mortality rate and morbidity with time. Different classes of drugs are available for the management of type 2 diabetes but were having certain limitations of their safety. Alphaglucosidase is a family of enzyme originated from the pancreas which plays a role in the anabolism of 80-90% of carbohydrate consumed into glucose. This glucose is absorbed into the blood and results in frank postprandial hyperglycemia and worsens the conditions of diabetic patients which precipitate complications. Inhibition of these enzymes helps to prevent postprandial hyperglycemia and the formation of glycated end products. Alphaglucosidase inhibitors are reported to be more important in adequate control of type 2, but marketed drugs have various side effects, such as poor patient compliance and also expensive. This proves the needs for other class of drugs with better efficacy, safety, patient compliance and economic. In this review, we have emphasized the recent advances in the field of new alpha-glucosidase inhibitors with improved safety and pharmacological profile.

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Natural Alpha-Glucosidase Inhibitors: Therapeutic Implication and Structure- Activity Relation Ship

Letters in Drug Design & Discovery ◽

10.2174/1570180812666150918193508 ◽

2016 ◽

Vol 13 (7) ◽

pp. 605-637 ◽

Cited By ~ 1

Author(s):

Sanae Abid ◽

Ali Berraaouan ◽

Mohamed Bnouham

Keyword(s):

Therapeutic Implication ◽

Structure Activity ◽

Glucosidase Inhibitors ◽

Alpha Glucosidase

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Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase

Scientific Reports ◽

10.1038/s41598-021-91473-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Fariba Peytam ◽

Ghazaleh Takalloobanafshi ◽

Toktam Saadattalab ◽

Maryam Norouzbahari ◽

Zahra Emamgholipour ◽

...

Keyword(s):

Molecular Docking ◽

Docking Study ◽

Rat Small Intestine ◽

Molecular Docking Study ◽

Design Synthesis ◽

Mild Conditions ◽

Glucosidase Inhibitors ◽

Inhibitory Activities

AbstractIn an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their inhibitory activities against yeast α-glucosidase enzyme were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which encouraged us to perform further studies on α-glucosidase enzymes obtained from rat as a mammal source. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against both Saccharomyces cerevisiae α-glucosidase (IC50 = 16.4 ± 0.36 μM) and rat small intestine α-glucosidase (IC50 = 45.0 ± 8.2 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.

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Histochemistry and immunolocalisation of glucokinin in antidiabetic plants used in traditional Mexican medicine

European Journal of Histochemistry ◽

10.4081/ejh.2017.2782 ◽

2017 ◽

Cited By ~ 1

Author(s):

Guillermo Laguna-Hernández ◽

Carlos A. Rio-Zamorano ◽

Itzel G. Meneses-Ochoa ◽

Alicia E. Brechú-Franco

Keyword(s):

Medicinal Plants ◽

Public Health Problem ◽

Direct Application ◽

Glucosidase Inhibitors ◽

Naphthol Blue Black ◽

Bauhinia Variegata ◽

Alpha Glucosidase ◽

Antidiabetic Plants

Mexico is a megadiverse country that has 3,600 to 4,000 species of medicinal plants, of which approximately 800 are used to treat conditions related to diabetes mellitus (DM). DM is a chronic degenerative disease of energy metabolism that exists as two types: type 1 (DM1) and type 2 (DM2). DM is considered a public health problem that affects 7% of the Mexican population older than 20 years. DM is clinically controlled with hypoglycaemic drugs, alpha-glucosidase inhibitors, insulin secretion stimulants or the direct application of insulin. The hypoglycaemic effectiveness of specific molecules has been determined only for some medicinal plants in Mexico used to treat DM2. The presence of molecules called glucokinins, wich are similar to animal insulin molecules, has been reported in some plant species; glucokinins act as both growth factors and regulators of glucose metabolism in plants. Therefore, we hypothesized that the hypoglycaemic effectiveness of some of the popularly used species for the control of DM could be due to the presence of glucokinin, as reported for Bauhinia variegata. The goal of this work was to use histochemistry to detect, the accumulation of protein that is immunocytochemically compatible with glucokinin in slide sections of hypoglycaemic species used as remedies for DM2. The top fourteen most used medicinal plants in Mexico were selected for study via microscopic sections. Proteins were histochemically detected using naphthol blue black and Johansenâ€™s quadruple stain, and the immunocytochemical correspondence of the proteins with glucokinin was investigated using an insulin antibody. All species studied reacted positively to proteins and glucokinin in the same structures. The presence of glucokinin in these structures and the corresponding hypoglycaemic effects are discussed in the contex of the actions of other compounds.

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