Context: During diabetes mellitus, non-enzymatic reaction between amino groups of protein and carbonyl of reducing sugars (Millard reaction) is responsible for the major diabetic complications. Various efforts have been made to influence the process of protein glycation. Objectives: This review article provides an extensive survey of various studies published in scientific literature to understand the process of protein glycation and its measurement. Moreover, evaluation and identification of potential inhibitors (antiglycation agents) of protein glycation from natural and synthetic sources and their mechanism of action in vitro and in vivo are also addressed. Method: In this review article, the mechanism involved in the formation of advanced glycation end products (AGEs) is discussed, while in second and third parts, promising antiglycation agents of natural and synthetic sources have been reviewed, respectively. Finally, in vivo studies have been addressed. This review is mainly compiled from important databases such as Science, Direct, Chemical Abstracts, SciFinder, and PubMed. Results: During the last two decades, various attempts have been made to inhibit the process of protein glycation. New potent inhibitors of protein glycation belonging to different classes such as flavonoids, alkaloids, terpenes, benzenediol Schiff bases, substituted indol, and thio compounds have been identified. Conclusion: Antiglycation therapy will be an effective strategy in future to prevent the formation of AGEs for the management of late diabetic complications Current review article highlighted various compounds of natural and synthetic origins identified previously to inhibit the protein glycation and formation of AGEs in vitro and in vivo.

Detection of adulteration in carbohydrate-rich foods like fruit juices is particularly difficult because of the variety of the commercial sweeteners available that match the concentration profiles of the major carbohydrates in the foods. In present study, a new sensitive and robust assay using Fourier Transform Near-Infrared Spectroscopy (FT-NIRS) combined with partial least square (PLS) multivariate methods has been developed for detection and quantification of saccharin adulteration in different commercial fruit juice samples. For this investigation, six different commercially available fruit juice samples were intentionally adulterated with saccharin at the following percentage levels: 0%, 0.10%, 0.30%, 0.50%, 0.70%, 0.90%, 1.10%, 1.30%, 1.50%, 1.70% and 2.00% (weight/volume). Altogether, 198 samples were used including 18 pure juice samples (unadulterated) and 180 juice samples adulterated with saccharin. PLS multivariate methods including partial least-squares discriminant analysis (PLS-DA) and partial least-squares regressions (PLSR) were applied to the obtained spectral data to build models. The PLS-DA model was employed to differentiate between pure fruit juice samples and those adulterated with saccharin. The R² value obtained for the PLS-DA model was 97.90% with an RMSE error of 0.67%. Similarly, a PLS regression model was also developed to quantify the amount of saccharin adulterant in juice samples. The R² value obtained for the PLSR model was 97.04% with RMSECV error of 0.88%. The employed model was then cross-validated by using a test set which included 30% of the total adulterated juice samples. The excellent performance of the model was proved by the low root mean squared error of prediction value of 0.92% and the high correlation factor of 0.97. This newly developed method is robust, nondestructive, highly sensitive and economical.

Introduction: Dipeptidyl peptidase 4 (DPP-4) belongs to the family of serine proteases and is involved in the degradation of GLP-1 and GIP hormones, which enhance the production and release of insulin. Targeting DPP-4 inhibitors is increasingly being considered as promising paradigms to treat type 2 diabetes mellitus and therefore DPP-4 inhibitors are being considered as promising antidiabetic drugs. Areas covered: This review provides an overview of published patents describing natural and synthetic DPP-4 inhibitors from January 2015 to December 2018. Expert opinion: A fair number of new synthetic and natural DPP-4 inhibitors have been reported in last four years which describe the progress in the development of various heterocyclic scaffolds or heterocyclic hybrid compounds. As a result of this, many marketed DPP-4 inhibitors that have been approved by the appropriate governing bodies during the past decade, have been introduced as inhibitors. Molecular hybridization is an emerging idea in medicinal chemistry and therefore hybrid compounds of DPP-4 inhibitors with other DPP-4 inhibitors or with antidiabetic drugs should be formulated for a comprehensive evaluation. More detailed pharmacovigilance of DPP-4 inhibitors is required because this will address the pancreas-related adverse events as well as their impact on cardiovascular outcomes via long-term studies.

Lycium shawii Roem. & Schult and resin of Aloe vera (L.) BURM. F. are commonly used in Omani traditional medication against various ailments. Herein, their antiproliferative and antioxidant potential was explored. Bioassay-guided fractionation of the methanol extract of both plants led to the isolation of 14 known compounds, viz., 1–9 from L. shawii and 10–20 from A. vera. Their structures were confirmed by combined spectroscopic techniques including 1D (¹H and ¹³C) and 2D (HMBC, HSQC, COSY) nuclear magnetic resonance (NMR), and electrospray ionization-mass spectrometry (ESI-MS). The cytotoxic potential of isolates was tested against the triple-negative breast cancer cell line (MDA-MB-231). Compound 5 exhibited excellent antiproliferative activity in a range of 31 μM, followed by compounds 1–3, 7, and 12, which depicted IC₅₀ values in the range of 35–60 μM, while 8, 6, and 9 also demonstrated IC₅₀ values >72 μM. Subsequently, in silico target fishing was applied to predict the most potential cellular drug targets of the active compounds, using pharmacophore modeling and inverse molecular docking approach. The extensive in silico analysis suggests that our compounds may target carbonic anhydrase II (CA-II) to exert their anticancer activities. When tested on CA-II, compounds 5 (IC₅₀ = 14.4 µM), 12 (IC₅₀ = 23.3), and 2 (IC₅₀ = 24.4 µM) showed excellent biological activities in vitro. Additionally, the ethyl acetate fraction of both plants showed promising antioxidant activity. Among the isolated compounds, 4 possesses the highest antioxidant (55 μM) activity followed by 14 (241 μM). The results indicated that compound 4 can be a promising candidate for antioxidant drugs, while compound 5 is a potential candidate for anticancer drugs.

A series of 2-thio- and 2-seleno-acetamides bearing the benzenesulfonamide moiety were evaluated as Carbonic Anhydrase (CA, EC 4.2.1.1) inhibitors against different pathogenic bacteria such as the Vibrio cholerae (VchCA-α and VchCA-β), Burkholderia pseudomallei (BpsCA-β and BpsCA-γ), Mycobacterium tuberculosis (Rv3723-β) and the Salmonella enterica serovar Typhimurium (StCA2-β). The molecules represent interesting leads worth developing as innovative antibacterial agents since they possess new mechanism of action and isoform selectivity preferentially against the bacterial expressed CAs. The identification of potent and selective inhibitors of bacterial CAs may lead to tools also useful for deciphering the physiological role(s) of such proteins.