Exploring efficacy of indole-based dual inhibitors for α-glucosidase and α-amylase enzymes: In silico, biochemical and kinetic studies.

α-Glucosidase and α-amylase are enzymes which are associated with diabetic II. These enzymes break macromolecules of sugar into monosugar molecules which is soluble in body, hence increase the sugar level in blood. There is need to develop economical and save inhibitors to prevent them from breaking sugar macromolecules to soluble molecules which will control the level of sugar in blood. Therefore, we synthesized indole-based derivatives (1-18) and evaluated as dual inhibitor for α-glucosidase and α-amylase. These chemical scaffolds were built with variation in aryl ring which were found active with good to moderate activity for α-glucosidase having IC50 value ranging from 13.99 ± 0.10 to 59.09 ± 0.30 µM when compared with standard acarbose with IC50 of 11.29 ± 0.10 µM; for α-amylase IC50 value ranging from 13.14 ± 0.10 to 58.99 ± 0.30 µM when compared with the standard acarbose with IC50 of 11.12 ± 0.10 µM. Structure activity relationship (SAR) has been established for all compounds. Enzymatic kinetic study and molecular docking study have been carried out to investigate the binding interactions α-glucosidase and α-amylase enzyme.

2'-Aryl and 4'-arylidene substituted pyrazolones: As potential α-amylase inhibitors.

Acarbose and voglibose are well-known α-amylase inhibitors used for the management of type-II diabetes mellitus. Unfortunately, these well-known and clinically used inhibitors are also associated with several adverse effects. Therefore, there is still need to develop the safer therapy. Despite of a broad spectrum of biological significances of pyrazolone, it is infrequently evaluated for α-amylase inhibition. Current study deals with the synthesis and biological screening of aryl and arylidene substituted pyrazolones 1-18 for their potential α-amylase inhibitory activity. Structures of synthetic derivatives 1-18 were identified by different spectroscopic techniques. All compounds 1-18 (IC50 = 1.61 ±â€¯0.16 µM to 2.38 ±â€¯0.09 µM) exhibited significant to moderate inhibitory potential when compared to standard acarbose (IC50 = 1.46 ±â€¯0.26 µM). A number of derivatives including 8-12 (IC50 = 1.68 ±â€¯0.1 µM to 1.97 ±â€¯0.07 µM) and 14-16 (IC50 = 1.61 ±â€¯0.16 µM to 1.93 ±â€¯0.07 µM) were found to be significantly active. Limited SAR suggested that different substitutions on compounds do not have any significant effect on the inhibitory potential. Compounds were found to be mixed-type inhibitors revealed by kinetic studies. However, in silico study was identified a number of key features participating in the interaction with the binding site of α-amylase enzyme.

Effect of Paclitaxel-Loaded PLGA Nanoparticles on MDA-MB Type Cell Lines: Apoptosis and Cytotoxicity Studies.

BACKGROUND: Triple-Negative Breast Cancer is an aggressive type of breast cancer, which is not treatable by chemotherapy drugs, due to the lack of Estrogen Receptor (ER), Progesterone Receptor (PR) expression and Human Epidermal Growth Factor Receptor 2 (HER2) on the cell surface. OBJECTIVE: The aim of this study was to compare the effect of paclitaxel loaded PLGA nanoparticle (PTX-NPs) on the cytotoxicity and apoptosis of the different MDA-MB type of cell lines. METHOD: PTX-NPs were prepared by nanoprecipitation method and characterized earlier. The cytotoxicity of PTX-NPs was evaluated by MTT and LDH assay, later apoptosis was calculated by flow cytometry analysis. RESULTS: The prepared NP size of 317.5 nm and zetapontial of -12.7 mV showed drug release of 89.1 % at 48 h. MDA-MB-231 type cell showed significant cytotoxicity by MTT method of 47.4 ± 1.2 % at 24 h, 34.6 ± 0.8 % at 48 h and 23.5 ± 0.5 % at 72 h and LDH method of 35.9 ± 1.5 % at 24 h, 25.4 ± 0.6 % at 48 h and 19.8 ± 2.2 % at 72 h with apoptosis of 47.3 ± 0.4 %. CONCLUSION: We have found that PTX-NPs showed the cytotoxic effect on all the MDA-MB cancer cell lines and showed potent anticancer activities against MDA-MB-231 cell line via induction of apoptosis.

Updated Regulatory Considerations for Nanomedicines.

BACKGROUND: Nanomedicine is a branch which deals with medicinal products, devices, nonbiological complex drugs and antibody-nanoparticle conjugates and general health products that are manufactured using nanotechnology. OBJECTIVE: Nano-medicine provides the same efficacies as traditional medicines owing to their improved solubility and bioavailability with reduced dosages. However, there are currently safety concerns due to the difficulties related to nanomaterial characterization; this might be the reason for unawareness of such medicines among the patients. The absence of clear regulatory guidelines further complicates matters, as it makes the path to registering them with regulatory bodies difficult. However, some products have overcome these obstacles and have been registered. While there are many international initiatives to harmonize the regulatory requirements and helps the industry to determine the most important characteristics that influence in vivo product performance. CONCLUSION: This review focuses on the various types of nanopharmaceuticals, and developments process with strategies tailored to upcoming regulations may satisfy the patients' needs.