IN SILICO DESIGN, SYNTHESIS, CHARACTERIZATION, IN VITRO ANTI-INFLAMMATORY, AND ANTIOXIDANT STUDIES OF 4-ARYL-4H-CHROMENE DERIVATIVES
Objective: The objective of the study was to explore in silico design, preparation, characterization, and evaluation in vitro of some novel 4H-chromene derivatives as anti-inflammatory and antioxidant agents.
Methods: 4-phenyl-4H chromene derivatives were imperiled to in silico modeling studies at the molecular level. The ligands were docked against cyclooxygenase-2 (COX-2) receptor targets using Argus Lab. Based on the result, the derivatives were selected for wet lab synthesis. A highly efficient multicomponent reaction of 4H chromene was carried out by one-step condensation of aldehyde with malononitrile and resorcinol without catalyst in water under ultrasound irradiation. The prepared compounds were characterized by noting their melting point, ultraviolet (UV) spectroscopy, infrared (IR) spectroscopy, and thin layer chromatography (TLC) and were scrutinized for its in vitro anti-inflammatory and antioxidant activitives by in vitro cell culture studies. IR spectra of the two compounds were analyzed and studied. Thus, using melting point, TLC and UV spectroscopy the synthesized compounds were found to be pure and identified chemically. The synthesized compounds were then screened for in vitro antioxidant (by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide free radical scavenging) activity and anti-inflammatory activity by Raw 264.7 cell lines.
Result: From the study, it was noticed that chemical structure-2 showed better antioxidant and anti-inflammatory activitives than chemical structure. In the 4-phenyl-4H chromene derivatives, hydroxyl substitution at 7th position and electronegative halogen at 4th position showed better antioxidant and anti-inflammatory activities.
Conclusion: The results disclosed that these synthesized derivatives be likely to have moderate action against COX-2 mediated diseases, thereby it may lessen inflammation and agony because of its antioxidant and anti-inflammatory activitives.
2. Thomas NA, Zachariah SM. Pharmacological activities of chromene derivatives: An overview. Asian J Pharm Clin Res 2013;6(2):11-5.
3. Hwang PA, Chien SY, Chan YL, Lu MK, Wu CH, Kong ZL, et al. Inhibition of lipopolysaccharide (LPS) - Induced inflammatory responses by Sargassum hemiphyllums sulphated polysaccharide extract in RAW 264.7 macrophage cells. J Agric Food Chem 2011;59(5):2062-8.
4. Mladenovic M, Mihailovic M, Bogojevic D, Matic S, Niciforovic N, Mihailovic V, et al. In vitro antioxidant activity of selected 4-hydroxy-chromene-2-one derivatives-SAR, QSAR and DFT studies. Int J Mol Sci 2011;12(5):2822-41.
5. Vane JR, Bakhle YS, Botting RM. Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol 1998;20(1):97-120.
6. Luche JL. Synthetic Organic Sonochemistry. New York: Plenum Press; 1998.
7. Banitaba SH, Safari J, Khalili SD. Ultrasound promoted one-pot synthesis of 2-amino-4,8-dihydropyrano[3,2-b]pyran-3-carbonitrile scaffolds in aqueous media: A complementary â€˜green chemistryâ€™ tool to organic synthesis. Ultrason Sonochem 2013;20(1):401-7.
8. Mohan H. Textbook of Pathology. New Delhi: Jaypee Brothers Medical Publishers; 2010.
9. Young IS, Woodside JV. Antioxidant in health and disease. J Clin Pathol 2001;54(3):176-86.
10. Sekhar AS, Saranya TS, Baskar V, Manakadan AA. In silico approach of apoptosis inducing ability of different indole derivatives by interaction with caspase9. Int J Pharm Sci Rev Res 2016;40(2):92-102.
11. Chandran D, Pappachen LK, Prathap M, Jinsha MJ, Jilsha G. In silico drug design and molecular docking studies of some novel benzothiazole derivatives as anti-cancer and anti-inflammatory agents. Int J Pharm Pharm Sci 2014;6(2):203-8.
12. Polamarashetty A, Kakularam KR, Pallu R. Structure and ligand based drug design strategies in the development of novel 5-LOX inhibitors. Curr Med Chem 2012;19(22):3763-78.
13. Lipinski CA. Drug-like propeties and the causes of poor solubility and poor permeability. Am J Pharmacol Toxicol 2000;44:235-49.
14. Safari J, Heydarian M, Zarnegar Z. Synthesis of 2-amino-7-hydroxy- 4H-chromene derivatives under ultrasound irradiation: A rapid procedure without catalyst. Arab J Chem 2013;???:???.
15. Kemnitzer W, Drewe J, Jianq S, Zhanq H, Wanq Y, Zhao J, et al. Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell and caspase-based high-throughput screening assay. 1. Structure - Activity relationship of the 4-aryl group. J Med Chem 2004;47(25):6299-310.
16. Javanshir S, Safari M, Dekamin MG. A facile and green three-component synthesis of 2-amino-3-cyano-7-hydroxy-4H-chromenes on grinding. Sci Iran Trans C Chem Eng 2014;21(3):742.
17. Gennaro AR. Remingtonâ€™s Pharmaceutical Sciences. 17th ed. Easton: Mack Publishing Company; 1985.
18. Khairullina VR, Gerchikov AY, Allina E, Drevko YB, Yulsaeva A. Drevko BI. Antioxidant properties of some 7, 8-benzo-5, 6-dihydro (4H) selenochromene derivatives. Kinetcatal 2013;54(1):14-7.
19. Srokaz S, Cisowki W. Hydrogen peroxidase scavenging antioxidant and anti-radical activity of some phenolic acids. Food Chem Toxicol 2003;41(6):753.
20. Kumar HK, Navyashree SN, Rakshitha SR, Chauhan JB. Studies on the free radical scavenging activity of Syagrus romanzoffiana. Int J Pharm 2012;3(2):81-4.
21. Nair AJ, Soman P, George A, Surendran SA. Formulation of Myristica fragrans (Nutmeg) topical gel and its in vitro evaluation for antinflammatory activity. Int J Pharm Technol 2016;8(1):11065-76.
22. Futaki N, Takahasi S, Yokoyama M, Arai I, Higuchi S, Otomo S. NS-398, a new anti-inflammatory agent, selectively inhibits prostaglandin G/H synthase/cyclooxygenase (COX-2) activity in vitro. Prostaglandins 1994;47(1):55-9.
23. Patil BR, Sawant DS. Synthesis, docking studies and evaluation of antimicrobial and in vitro antiproliferative activity of 5H chromene 4, 3-D pyrimidin-2-amine derivatives. Int J Pharm Pharm Sci 2015;7(2):304-8.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.