ε-Poly-l-lysine: A Naturally Occurring Biodegradable Polypeptide for Selective Detection of 5-Nitroimidazole Antibiotics in Animal Products and Living Cells via Fluorescence.

The 5-nitroimidazole (5-NI) class of antibiotics, such as metronidazole, ornidazole, secnidazole, and tinidazole, are widely used to prevent bacterial infection in humans and livestock industries. However, their overuse contaminates the farmed animal products and water bodies. Hence, a selective, sensitive, and cost-effective method to detect 5-NI antibiotics is the need of the hour. Herein, we report a rapid, inexpensive, and efficient sensing system to detect 5-NI drugs using an as-prepared solution of ε-poly-l-lysine (ε-PL), a naturally occurring and biodegradable homopolypeptide that has an intrinsic fluorescence via clustering-triggered emission. The low nanomolar detection limit (3.25-3.97 nM) for the aforementioned representative 5-NI drugs highlights the sensitivity of the system, outperforming most of the reported sensors alike. The resulting fluorescence quenching was found to be static in nature. Importantly, excellent recovery (100.26-104.41%) was obtained for all real samples and animal products tested. Visual detection was demonstrated by using paper strips and silica gel for practical applications. Furthermore, ε-PL could detect 5-NI antibiotics in living 3T3-L1 mouse fibroblast cells via cellular imaging. Taken together, the present work demonstrates the detection of 5-NI antibiotics using a biocompatible natural polypeptide, ε-PL, and represents a simple and inexpensive analytical tool for practical application.

Novel molecular hybrids of EGCG and quinoxaline: Potent multi-targeting antidiabetic agents that inhibit α-glucosidase, α-amylase, and oxidative stress.

Diabetes mellitus is a multifactorial disease and its effective therapy often demands several drugs with different modes of action. Herein, we report a rational design and synthesis of multi-targeting novel molecular hybrids comprised of EGCG and quinoxaline derivatives that can effectively inhibit α-glucosidase, α-amylase as well as control oxidative stress by scavenging ROS. The hybrids showed superior inhibition of α-glucosidase along with similar α-amylase inhibition as compared to standard drug, acarbose. Most potent compound, 15c showed an IC50 of 0.50 µM (IC50 of acarbose 190 µM) against α-glucosidase. Kinetics studies with 15c revealed a competitive inhibition against α-glucosidase. Binding affinity of 15c (-9.5 kcal/mol) towards α-glucosidase was significantly higher than acarbose (-7.7 kcal/mol). 15c exhibited remarkably high antioxidant activity (IC50 = 18.84 µM), much better than vitamin C (IC50 = 33.04 µM). Of note, acarbose shows no antioxidant activity. Furthermore, α-amylase activity was effectively inhibited by 15c with an IC50 value of 16.35 µM. No cytotoxicity was observed for 15c (up to 40 µM) in MCF-7 cells. Taken together, we report a series of multi-targeting molecular hybrids capable of inhibiting carbohydrate hydrolysing enzymes as well as reducing oxidative stress, thus representing an advancement towards effective and novel therapeutic approaches for diabetes.