Background: Among the millions of people around the world, the most prevalent metabolic disorder is diabetes mellitus. Due to the drawbacks which are associated with commercially available antidiabetic agents, new therapeutic approaches are needed to be considered. Alpha-amylase is a membrane- bound enzyme which is responsible for the breakdown of polysaccharides such as starch to monosaccharides which can be absorbed. Methods: We searched the scientific database using alpha-amylase, diabetes, antidiabetic agents as the keywords. Here in, only peer-reviewed research articles were collected which were useful to our current work. Results: To overcome the research gap, the alpha-amylase enzyme is regarded as a good target for antidiabetic agents to design the drug and provide an alternate approach for the treatment of type 2 diabetes mellitus. Basically, alpha-amylase inhibitors are classified into two groups: proteinaceous inhibitors, and non-proteinaceous inhibitors. Recently, non-proteinaceous inhibitors are being explored which includes chalcones, flavones, benzothiazoles, etc. as the potential antidiabetic agents. Conclusion: Herein, we discuss various potential antidiabetic agents which are strategically targeted alpha-amylase enzyme. These are having lesser side effects as compared to other antidiabetic agents, and are proposed to prevent the digestion and absorption of glucose leading to a decrease in the blood glucose level.

The aim of this study was to enhance the dissolution profile of the combination of glipizide and atorvastatin used for simultaneous treatment of hyperglycemia and hyperlipidemia. The strategy to formulate coamorphous glipizide-atorvastatin binary mixture was explored to achieve enhancement in dissolution. The coamorphous glipizide-atorvastatin mixtures (1:1, 1:2 and 2:1) were prepared by cryomilling and characterized with respect to their dissolution profiles, preformulation parameters and physical stability. Amorphization was found to be possible by cryomilling at various tried ratios of the two drugs. The data obtained from glass transition temperatures and from Raman spectroscopy point toward practically no interaction between the two drugs. The dissolution studies revealed the highest enhancement in dissolution profiles of cryomilled coamorphous mixtures containing GPZ:ATV in ratios 1:1 (B-5) and 2:1 (B-7). These two mixtures were, therefore, subjected to studies for the evaluation of precompression parameters in order to find their amenability to satisfactory compression into tablet dosage form. The selected formulation was found to be stable when subjected to accelerated stability testing at 40°. C/75% RH for six months as per ICH guidelines. Based on all these studies, it was concluded that GPZ:ATV (1:1) combination may be able to provide an effective therapy for the comorbidities of hyperglycemia and hyperlipidemia.

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Present study deciphers preparation of co-crystals of lipophilic glipizide by using four different acids, oxalic, malonic, stearic, and benzoic acids, in order to achieve enhanced solubility and dissolution along with stability. All co-crystals were prepared by dissolving drug and individual acids in the ratio of 1:0.5 in acetonitrile at 60-70°C for 15 min, followed by cooling at room temperature for 24 h. FT-IR spectroscopy revealed no molecular interaction between acids and drug as the internal structure and their geometric configurations remain unchanged. Differential scanning calorimetry revealed closer melting points of raw glipizide and its co-crystals, which speculates absence of difference in crystallinity as well as intermolecular bonding of the co-crystals and drug. PXRD further revealed that all the co-crystals were having similar crystallinity as that of raw glipizide except glipizide-malonic acid co-crystals. This minor difference in the relative intensities of some of the diffraction peaks could be attributed to the crystal habit or crystal size modification. SEM revealed difference in the crystal morphology for all the co-crystals. Micromeritic, solubility, dissolution, and stability data revealed that among all the prepared co-crystals, glipizide-stearic acid co-crystals were found superior. Hence, it was concluded that glipizide-stearic acid co-crystals could offer an improved drug design strategy to overcome dissolution and bioavailability related challenges associated with lipophilic glipizide.

A series of 2-chloro-5-[(4-chlorophenyl)sulfamoyl]-N-(alkyl/aryl)-4-nitrobenzamide derivatives (5a-5v) has been synthesized and confirmed by physicochemical(R f , melting point) and spectral means (IR, 1 HNMR, 13 CNMR). The results of in vitro antidiabetic study against α-glucosidase indicated that compound 5o bearing 2-CH 3-5-NO 2 substituent on phenyl ring was found to be the most active compound against both enzymes. The electron donating (CH 3) group and electron withdrawing (NO 2) group on a phenyl ring highly favoured the inhibitory activity against these enzymes. The docking simulations study revealed that these synthesized compounds displayed hydrogen bonding, electrostatic and hydrophobic interactions with active site residues. The structure activity relationship studies of these compounds were also corroborated with the help of molecular modeling studies. Molecular dynamic simulations have been done for top most active compound for validating its α-glucosidase and α-amylase inhibitory potential, RMSD analysis of ligand protein complex suggested the stability of top most active compound 5o in binding site of target proteins. In silico ADMET results showed that synthesized compounds were found to have negligible toxicity, good solubility and absorption profile as the synthesized compounds fulfilled Lipinski's rule of 5 and Veber's rule.