Syntheses, in vitro, and in silico studies of rhodanine-based schiff bases as potential α-amylase inhibitors and radicals (DPPH and ABTS) scavengers.

A two-step reaction method was used to synthesize a series of rhodanine-based Schiff bases (2-33) that were characterized using spectroscopic techniques. All compounds were assessed for α-amylase inhibitory and radical scavenging (DPPH and ABTS) activities. In comparison to the standard acarbose (IC50 = 9.08 ± 0.07 µM), all compounds demonstrated good to moderate α-amylase inhibitory activity (IC50 = 10.91 ± 0.08-61.89 ± 0.102 µM). Compounds also demonstrated significantly higher DPPH (IC50 = 10.33 ± 0.02-96.65 ± 0.03 µM) and ABTS (IC50 = 12.01 ± 0.12-97.47 ± 0.13 µM) radical scavenging activities than ascorbic acid (DPPH, IC50 = 15.08 ± 0.03 µM; ABTS, IC50 = 16.09 ± 0.17 µM). The limited structure-activity relationship (SAR) suggests that the position and nature of the substituted groups on the phenyl ring have a vital role in varying inhibitory potential. Among the series, compounds with an electron-withdrawing group at the para position showed the highest potency. Kinetic studies revealed that the compounds followed a competitive mode of inhibition. Molecular docking results are found to agree with experimental findings, showing that compounds reside in the active pocket due to the main rhodanine moiety.

Dihydroquinazolin-4(1H)-one derivatives as novel and potential leads for diabetic management.

A variety of dihydroquinazolin-4(1H)-one derivatives (1-37) were synthesized via "one-pot" three-component reaction scheme by treating aniline and different aromatic aldehydes with isatoic anhydride in the presence of acetic acid. Chemical structures of compounds were deduced by different spectroscopic techniques including EI-MS, HREI-MS, 1H-, and 13C-NMR. Compounds were subjected to α-amylase and α-glucosidase inhibitory activities. A number of derivatives exhibited significant to moderate inhibition potential against α-amylase (IC50 = 23.33 ± 0.02-88.65 ± 0.23 µM) and α-glucosidase (IC50 = 25.01 ± 0.12-89.99 ± 0.09 µM) enzymes, respectively. Results were compared with the standard acarbose (IC50 = 17.08 ± 0.07 µM for α-amylase and IC50 = 17.67 ± 0.09 µM for α-glucosidase). Structure-activity relationship (SAR) was rationalized by analyzing the substituents effects on inhibitory potential. Kinetic studies were implemented to find the mode of inhibition by compounds which revealed competitive inhibition for α-amylase and non-competitive inhibition for α-glucosidase. However, in silico study identified several important binding interactions of ligands (synthetic analogues) with the active site of both enzymes.

Green Synthesis and Characterization of Silver Nanoparticles Using Spondias mombin Extract and Their Antimicrobial Activity against Biofilm-Producing Bacteria.

Multidrug resistant bacteria create a challenging situation for society to treat infections. Multidrug resistance (MDR) is the reason for biofilm bacteria to cause chronic infection. Plant-based nanoparticles could be an alternative solution as potential drug candidates against these MDR bacteria, as many plants are well known for their antimicrobial activity against pathogenic microorganisms. Spondias mombin is a traditional plant which has already been used for medicinal purposes as every part of this plant has been proven to have its own medicinal values. In this research, the S. mombin extract was used to synthesise AgNPs. The synthesized AgNPs were characterized and further tested for their antibacterial, reactive oxygen species and cytotoxicity properties. The characterization results showed the synthesized AgNPs to be between 8 to 50 nm with -11.52 of zeta potential value. The existence of the silver element in the AgNPs was confirmed with the peaks obtained in the EDX spectrometry. Significant antibacterial activity was observed against selected biofilm-forming pathogenic bacteria. The cytotoxicity study with A. salina revealed the LC50 of synthesized AgNPs was at 0.81 mg/mL. Based on the ROS quantification, it was suggested that the ROS production, due to the interaction of AgNP with different bacterial cells, causes structural changes of the cell. This proves that the synthesized AgNPs could be an effective drug against multidrug resistant bacteria.

Synthesis, in vitro α-amylase inhibitory, and radicals (DPPH & ABTS) scavenging potentials of new N-sulfonohydrazide substituted indazoles.

Over-expression of α-amylase enzyme causes hyperglycemia which lead to many physiological complications including oxidative stress, one of the most commonly associated problem with diabetes mellitus. Marketed α-amylase inhibitors such as acarbose, voglibose, and miglitol used to treat type-II diabetes mellitus, but also linked to several harmful effects. Therefore, it is essential to explore new and nontoxic antidiabetic agents with additional antioxidant properties. In this connection, a series of new N-sulfonohydrazide substituted indazoles 1-19 were synthesized by multistep reaction scheme and assessed for in vitro α-amylase inhibitory and radical (DPPH and ABTS) scavenging properties. All compounds were fully characterized by different spectroscopic techniques including 1H, 13C NMR, EI-MS, HREI-MS, ESI-MS, and HRESI-MS. Compounds showed promising α-amylase inhibitory activities (IC50 = 1.23 ±â€¯0.06-4.5 ±â€¯0.03 µM) as compared to the standard acarbose (IC50 1.20 ±â€¯0.09 µM). In addition to that all derivatives were found good to moderate scavengers of DPPH (IC50 2.01 ±â€¯0.13-5.3 ±â€¯0.11) and ABTS (IC50 = 2.34 ±â€¯0.07-5.5 ±â€¯0.07 µM) radicals, in comparison with standard ascorbic acid having scavenging activities with IC50 = 1.99 ±â€¯0.09 µM, and IC50 2.03 ±â€¯0.11 µM for DPPH and ABTS radicals. In silico molecular docking study was conducted to rationalize the binding interaction of α-amylase enzyme with ligands. Compounds were observed as mixed type inhibitors in enzyme kinetic characterization.

New pyrrolopyridine-based thiazolotriazoles as diabetics inhibitors: enzymatic kinetics and in silico study.

Aim: To synthesize pyrrolopyridine-based thiazolotriazoles as a novel class of α-amylase and α-glucosidase inhibitors and to determine their enzymatic kinetics. Methodology: Pyrrolopyridine-based thiazolotriazole analogs (1-24) were synthesized and characterized through proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance and high-resolution electron ionization mass spectrometry. Results: All synthesized analogs displayed good inhibitory potential of α-amylase and α-glucosidase ranging 17.65-70.7 µM and 18.15-71.97 µM, respectively, compared with the reference drug, acarbose (11.98 µM and 12.79 µM). Analog 3 was the most potent among the synthesized analogs, having α-amylase and α-glucosidase inhibitory activity at 17.65 and 18.15 µM, respectively. The structure-activity relationship and binding modes of interactions between selected analogs were confirmed via docking and enzymatic kinetics studies. The compounds (1-24) were tested for cytotoxicity against the 3T3 mouse fibroblast cell line and were observed to be nontoxic.

Mechanistic insights into the beneficial effects of curcumin on insulin resistance: Opportunities and challenges.

The past couple of decades in particular have seen a rapid increase in the prevalence of type 2 diabetes mellitus (T2DM), a debilitating metabolic disorder characterised by insulin resistance. The insufficient efficacy of current management strategies for insulin resistance calls for additional therapeutic options. The preponderance of evidence suggests potential beneficial effects of curcumin on insulin resistance, while modern science provides a scientific basis for its potential applications against the disease. Curcumin combats insulin resistance by increasing the levels of circulating irisin and adiponectin, activating PPARγ, suppressing Notch1 signalling, and regulating SREBP target genes, among others. In this review, we bring together the diverse areas pertaining to our current understanding of the potential benefits of curcumin on insulin resistance, associated mechanistic insights, and new therapeutic possibilities.

Synthesis of indole derivatives as diabetics II inhibitors and enzymatic kinetics study of α-glucosidase and α-amylase along with their in-silico study.

In this study, we have investigated a series of indole-based compounds for their inhibitory study against pancreatic α-amylase and intestinal α-glucosidase activity. Inhibitors of carbohydrate degrading enzymes appear to have an essential role as antidiabetic drugs. All analogous exhibited good to moderate α-amylase (IC50 = 3.80 to 47.50 µM), and α-glucosidase inhibitory interactions (IC50 = 3.10-52.20 µM) in comparison with standard acarbose (IC50 = 12.28 µM and 11.29 µM). The analogues 4, 11, 12, 15, 14 and 17 had good activity potential both for enzymes inhibitory interactions. Structure activity relationships were deliberated to propose the influence of substituents on the inhibitory potential of analogues. Docking studies revealed the interaction of more potential analogues and enzyme active site. Further, we studied their kinetic study of most active compounds showed that compounds 15, 14, 12, 17 and 11 are competitive for α-amylase and non- competitive for α-glucosidase.

Synthesis of benzotriazoles derivatives and their dual potential as α-amylase and α-glucosidase inhibitors in vitro: Structure-activity relationship, molecular docking, and kinetic studies.

Benzotriazoles (4-6) were synthesized which were further reacted with different substituted benzoic acids and phenacyl bromides to synthesize benzotriazole derivatives (7-40). The synthetic compounds (7-40) were characterized via different spectroscopic techniques including EI-MS, HREI-MS, 1H-, and 13C NMR. These molecules were examined for their anti-hyperglycemic potential hence were evaluated for α-glucosidase and α-amylase inhibitory activities. All benzotriazoles displayed moderate to good inhibitory activity in the range of IC50 values of 2.00-5.6 and 2.04-5.72 µM against α-glucosidase and α-amylase enzymes, respectively. The synthetic compounds were divided into two categories "A" and "B", in order to understand the structure-activity relationship. Compounds 25 (IC50 = 2.41 ±â€¯1.31 µM), (IC50 = 2.5 ±â€¯1.21 µM), 36 (IC50 = 2.12 ±â€¯1.35 µM), (IC50 = 2.21 ±â€¯1.08 µM), and 37 (IC50 = 2.00 ±â€¯1.22 µM), (IC50 = 2.04 ±â€¯1.4 µM) with chloro substitution/s at aryl ring were found to be most active against α-glucosidase and α-amylase enzymes. Molecular docking studies on all compounds were performed which revealed that chloro substitutions are playing a pivotal role in the binding interactions. The enzyme inhibition mode was also studied and the kinetic studies revealed that the synthetic molecules have shown competitive mode of inhibition against α-amylase and non-competitive mode of inhibition against α-glucosidase enzyme.

Anti-EGFR anchored paclitaxel loaded PLGA nanoparticles for the treatment of triple negative breast cancer. In-vitro and in-vivo anticancer activities.

The aim of the present study is to analyze the viability of anti-EGFR anchored immunonanoparticle (INP) bearing Paclitaxel (PTX) to specifically bind the EGFR protein on the TNBC cells. The NP was prepared by nanoprecipitation and characterized the particle size, charge, entrapment of drug and release of it. The anti-EGFR anchored and the integrity was confirmed by SDS-PAGE. Cytotoxicity and NPs cellular uptake was analyzed with MDA-MB-468 type cancer cells and the EGFR expression was confirmed by PCR, qualitatively and quantitatively. The in-vivo antitumor activity of INP was determined by using athymic mice model and targeting efficiency was measured by calculating the PTX accumulation in the tumor plasma. The prepared INP with the size of 336.3 nm and the charge of -3.48 mV showed sustained drug release upto 48 h. The INP showed significant reduction of cancer cell viability of 10.6% for 48 h with 93 fold higher PTX accumulation in the tumor plasma compared with NPs. Based on these reports, we recommend that anti-EGFR anchored PTX loaded NP may have the ability to target the TNBC cells and improve the therapeutic action and subsidize the side effects of PTX for the treatment of TNBC.