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Design and in silico modeling of Indoloquinoxaline incorporated keratin nanoparticles for modulation of glucose metabolism in 3T3-L1 adipocytes
Authors:Selvaraj Kunjiappan  Panneerselvam Theivendren  Parasuraman Pavadai  Saravanan Govindaraj  Murugesan Sankaranarayanan  Balasubramanian Somasundaram  Sankarganesh Arunachalam  Sureshbabu Ram Kumar Pandian  Damodar Nayak Ammunje
Affiliation:1. Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil, Tamil Nadu, India;2. Department of Pharmaceutical Chemistry, Saraswathi College of Pharmacy, Hapur, Uttar Pradesh, India;3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M S Ramaiah University of Applied Sciences, Bengaluru, Karnataka, India;4. Department of Pharmaceutical Chemistry, MNR College of Pharmacy, Sangareddy, Telangana, India;5. Department of Pharmacy, Birla Institute of Technology and Science, Pilani, India;6. Sir CV Raman-KS Krishnan International Research Center, Kalasalingam Academy of Research and Education, Krishnankoil, Tamil Nadu, India;7. Department of Pharmacology, Faculty of Pharmacy, M S Ramaiah University of Applied Sciences, Bengaluru, Karnataka, India
Abstract:The following study was done to assess the glucose utilizing efficiency of Indoloquinoxaline derivative incorporated keratin nanoparticles (NPs) in 3T3-L1 adipocytes. Indoloquinoxaline derivative had wide range of biological activities including antidiabetic activity. In this view, Indoloquinoxaline moiety containing N, N-dimethyl (3-fluoro-6H-indolo [3,2-b] quinoxalin-6-yl) methanamine compound was designed and synthesized, and further it is incorporated into keratin nanoparticles. The formulated NPs, drug entrapment efficiency, releasing capacity, stability, and physicochemical properties were characterized by various spectral analyzer and obtained results of characterizations were confirmed the properties of NPs. The analysis of mechanism underlying the glucose utilization of NPs was examined through molecular docking with identified target, and observed in silico study reports shown strong interaction of NPs in the binding pockets of AMPK and PTP1B. Based on the in silico screening, the formulated NPs was performed for in vitro cellular viability and glucose uptake studies on 3T3-L1 adipocytes. Interestingly, 40 μg of NPs displayed 78.2 ± 2.76% cellular viability, and no cell death was observed at lower concentrations. Further, the concentration dependent glucose utilization was observed at different concentrations of NPs in 3T3-L1 adipocytes. The results of NPs (40 μg) on glucose utilization have revealed eminent result 58.56 ± 4.54% compared to that of Metformin (10 μM) and Insulin (10 μM). The identified results clearly indicated that Indoloquinoxaline derivative incorporated keratin NPs significantly increased glucose utilization efficiency and protect the cells against the insulin resistance.
Keywords:3T3-L1 adipocytes  glucose uptake  in silico modeling  Indoloquinoxaline  keratin nanoparticles
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