Designing and Synthesis of Flavonoids Derivatives and Screening of their Antimicrobial Activity
Antimicrobial drugs either kill microbes (microbicidal) or prevent the growth of microbes (microbistatic). The streptococcus mutans is a bacteria that found in the human mouth cavity. This bacterial strain produces plaque and acids that break down tooth enamel and cause dental caries. Gram positive cocci, facultatively anaerobic bacteria that forms rod-like chains. the chemical reaction of 2- hydroxyacetophenones with aromatic acylchloride occurs to form 1,3-diketones. This rearrangement reaction proceeds via enolate formation followed by acyl transfer. Then it cyclises into flavone.13 As the same of above scheme can be worked out as 2- Methoxybenzoyl Chloride is prepared by reaction of 2- methoxybenzoic acid with Thionyl chloride and DMF. 2-Methoxybenzoyl Chloride then added to mixture of 2- hydroxyacetophenone and pyridine, 2-[(2-Methoxybenzoyl)oxy]acetophenone thus obtained is treated with pyridine and KOH which gives1-(2-Hydroxyphenyl)-3-(2- methoxyphenyl)-propan1,3-dione. The result of study indicated that C5 [1-(2- hydroxyphenyl)-5-phenylpenta-2,4-dien-1-one]; is only inactive against Streptococcus mutans. All 3-hydroxyflavone derivatives exhibited their MIC to be in range of 250-125 µg/ml., 2,3-dihydroflavan-3-ol derivatives exhibited their MIC to be in range of 1000- 500 µg/ml. The chalcone derivatives exhibited their MIC to be at 250 µg/ml.
Keywords: Streptococcus mutans, flavonoids derivatives, MIC, 2,3-dihydroflavan-3-ol.
2. Halliwell B and Gutteridge J in Free Radicals in Biology and Medicine 2007.
3. Finaud J ; Sports Medicine 2006; 35 (4): 327-358
4. Hideo Ohashi, Tetsuya Kyogoku, Takahiro lshikawa, J Wood Sci 1999; 45:53-63
5. Haenen GR, Bast A. Nitric oxide radical scavenging of flavonoids. Methods Enzymol 1999; 301:490–503.
6. Shuji Kitagawa, Hiromi Sakamoto, and Hiromi Tano, Inhibitory Effects of Flavonoids on Free Radical-Induced Hemolysis andTheir Oxidative Effects on Hemoglobin, Chem. Pharm. Bull. 52(8), 2004; 999-1001.
7. Korkina LG, Afanas'ev IB. Antioxidant and chelating properties of flavonoids. Adv Pharmacol , 1997; 38:151–63
8. US patent: US 6346364 Zyang .
9. Kerry NL, Abbey M. Red wine and fractionated phenolic compounds prepared from red wine inhibit low density lipoprotein oxidation in vitro. Atherosclerosis, 1997; 135:93–102.
10. Shutenko Z, Henry Y, Pinard E, Influence of the antioxidant quercetin in vivo on the level of nitric oxide determined by electron paramagnetic resonance in rat brain during global ischemia and reperfusion. Biochem Pharmacol 1999; 57: 199–208.
11. Van Acker SA, Tromp MN, Haenen GR, van der Vijgh WJ, Bast A. Flavonoids as scavengers of nitric oxide radical. Biochem Biophys Res Commun, 1995; 214: 755–9.
12. Chang WS, Lee YJ, Lu FJ, Chiang HC., Inhibitory effects of flavonoids on xanthine oxidase. Anticancer Res, 1993; 13: 2165–70.
13. Manach C, Morand C, Texier O., Quercetin metabolites in plasma of rats fed diets containing rutin or quercetin. J Nutr, 1995; 125:1911–22.
14. Cos P, Ying L, Calomme M., Structure-activity relationship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers. J Nat Prod, 1998; 61:71–6.
15. Friesenecker B, Tsai AG, Allegra C, Intaglietta M., Oral administration of purified micronized flavonoid fraction suppresses leukocyte adhesion in ischemia-reperfusion injury: in vivo observations in the hamster skin fold. Int J Microcirc Clin Exp 1994; 14:50–5.
16. Cho, J.W. Cho, S.Y. Lee, S.R. Lee, K.S. Onion extract and quercetin induce matrix metalloproteinase-1 in vitro and in vivo. Int. J. Mol. Med. 2010; 25, 347–352. [PubMed]
17. Chuang, S.Y. Lin, Y.K.; Lin, C.F. Wang, P.W. Chen, E.L. Fang, J.Y. Elucidating the skin delivery of aglycone and glycoside flavonoids: How the structures affect cutaneous absorption. Nutrients 2017; 9, 1304.
18. Nagoba, B.S. Suryawanshi, N.M. Wadher, B. Selkar, S. Acidic environment and wound healing: A review. Wounds 2015; 27, 5–11. J. Clin. Med. 2020; 9, 109 15 of 17
19. Nagoba, B. Davane, M. Gandhi, R. Wadher, B. Suryawanshi, N. Selkar, S. Treatment of skin and soft tissue infections caused by Pseudomonas aeruginosa—A review of our experiences with citric acid over the past 20 years. Wound Med. 2017, 19:5–9.
20. Bessa, L.J. Fazii, P. Di Giulio, M. Cellini, L. Bacterial isolates from infected wounds and their antibiotic susceptibility pattern: Some remarks about wound infection. Int. Wound J. 2013; 12, 47–52.
21. Karpi nski, T.M. Efficacy of octenidine against Pseudomonas aeruginosa strains. Eur. J. Biol. Res. 2019; 9:135–140.
22. CLSI. Performance Standards for Antimicrobial Disk Susceptibility Tests. Approved Standard, 12th ed. CLSI document M02-A12, Clinical and Laboratory Standards Institute: Wayne, PA, USA, 2015 Volume 35, no 1.
23. EUCAST. MIC Determination of Non-Fastidious and Fastidious Organisms. Available online: http://www.eucast. org/ast_of_bacteria/mic_determination (accessed on 26 July 2019).
24. Karpi nski, T.M. Adamczak, A. Fucoxanthin—An antibacterial carotenoid. Antioxidants 2019, 8, 239.
25. Gao, Z. Shao, J. Sun, H. Zhong, W. Zhuang, W.; Zhang, Z. Evaluation of different kinds of organic acids and their antibacterial activity in Japanese Apricot fruits. Afr. J. Agric. Res. 2012; 7:4911–4918.
26. Su, Y. Ma, L. Wen, Y. Wang, H. Zhang, S. Studies of the in vitro antibacterial activities of several polyphenols against clinical isolates of methicillin-resistant Staphylococcus aureus. Molecules 2014; 19:12630–12639.
27. Blaskovich, M.A. Elliott, A.G. Kavanagh, A.M. Ramu, S. Cooper, M.A. In vitro antimicrobial activity of acne drugs against skin-associated bacteria. Sci. Rep. 2019; 9:14658.
28. Basile, A. Giordano, S. López-Sáez, J.A. Cobianchi, R.C. Antibacterial activity of pure flavonoids isolated from mosses. Phytochemistry 1999; 52:1479–1482.
29. Afifi, F.U. Abu-Dahab, R. Phytochemical screening and biological activities of Eminium spiculatum (Blume) Kuntze (family Araceae). Nat. Prod. Res. 2012, 26, 878–882.
30. Das, M.C. Sandhu, P. Gupta, P. Rudrapaul, P. De, U.C. Tribedi, P. Akhter, Y. Bhattacharjee, S. Attenuation of Pseudomonas aeruginosa biofilm formation by vitexin: A combinatorial study with azithromycin and gentamicin. Sci. Rep. 2016, 6, 23347.
31. Das, M.C. Das, A. Samaddar, S. Dawarea, A.V. Ghosh, C. Acharjee, S. Sandhu, P.; Jawed, J.J. De Utpal, C. Majumdar, S. et al. Vitexin alters Staphylococcus aureus surface hydrophobicity to interfere with biofilm 2 formation. bioRxiv 2018.
32. Awolola, G.V. Koorbanally, N.A. Chenia, H. Shode, F.O. Baijnath, H. Antibacterial and anti-biofilm activity of flavonoids and triterpenes isolated from the extracts of Ficus sansibarica Warb. subsp. Sansibarica (Moraceae) extracts. Afr. J. Tradit. Complem. Altern. Med. 2014, 11, 124–131.
33. Rammohan, A. Bhaskar, B.V. Venkateswarlu, N. Rao, V.L. Gunasekar, D. Zyryanov, G.V. Isolation of flavonoids from the flowers of Rhynchosia beddomei Baker as prominent antimicrobial agents and molecular docking. Microb. Pathog. 2019, 136, 103667.
34. Aderogba, M.A. Akinkunmi, E.O. Mabusela, W.T. Antioxidant and antimicrobial activities of flavonoid glycosides from Dennettia tripetala G. Baker leaf extract. Nig. J. Nat. Prod. Med. 2011, 15, 49–52.
35. Cottiglia, F. Loy, G. Garau, D. Floris, C. Casu, M. Pompei, R. Bonsignore, L. Antimicrobial evaluation of coumarins and flavonoids from the stems of Daphne gnidium L. Phytomedicine 2001, 8, 302–305.
36. Ali, H. Dixit, S. In vitro antimicrobial activity of flavanoids of Ocimum sanctum with synergistic effect of their combined form. Asian Pac. J. Trop. Dis. 2012, 2, S396–S398.
37. Celiz, G. Daz, M. Audisio, M.C. Antibacterial activity of naringin derivatives against pathogenic strains. J. Appl. Microbiol. 2011, 111, 731–738.
38. Akhtar, M.S. Hossain, M.A. Said, S.A. Isolation and characterization of antimicrobial compound from the stem-bark of the traditionally used medicinal plant Adenium obesum. J. Tradit. Complem. Med. 2017, 7, 296–300.
39. Singh, M. Govindarajan, R. Rawat, A.K.S. Khare, P.B. Antimicrobial flavonoid rutin from Pteris vittata L. against pathogenic gastrointestinal microflora. Am. Fern J. 2008, 98, 98–103.
40. Liu, H. Mou, Y. Zhao, J. Wang, J. Zhou, L. Wang, M. Wang, D. Han, J. Yu, Z. Yang, F. Flavonoids from Halostachys caspica and their antimicrobial and antioxidant activities. Molecules 2010, 15, 7933–7945. [CrossRef] [PubMed] J. Clin. Med. 2020, 9, 109 16 of 17
41. Banerjee, K. Banerjee, S. Das, S. Mandal, M. Probing the potential of apigenin liposomes in enhancing bacterial membrane perturbation and integrity loss. J. Colloid Interface Sci. 2015, 453, 48–59.
42. Ekambaram, S.P. Perumal, S.S. Balakrishnan, A. Marappan, N. Gajendran, S.S. Viswanathan, V. Antibacterial synergy between rosmarinic acid and antibiotics against methicillin-resistant Staphylococcus aureus. J. Intercult. Ethnopharmacol. 2016, 5, 358–363.
43. Smiljkovic, M. Stanisavljevic, D. Stojkovic, D. Petrovic, I. Vicentic, M.J. Popovic, J. Golic Grdadolnik, S. Markovic, D. Sankovic-Babice, S. Glamoclija, J. et al. Apigenin-7-O-glucoside versus apigenin: Insight into the modes of anticandidal and cytotoxic actions. EXCLI J. 2017, 16, 795–807.
44. Matejczyk, M. Swisłocka, R. Golonko, A. Lewandowski, W. Hawrylik, E. Cytotoxic, genotoxic and antimicrobial activity of caffeic and rosmarinic acids and their lithium, sodium and potassium salts as potential anticancer compounds. Adv. Med. Sci. 2018, 63, 14–21.
45. Ren, G. Xue, P. Sun, X. Zhao, G. Determination of the volatile and polyphenol constituents and the antimicrobial, antioxidant, and tyrosinase inhibitory activities of the bioactive compounds from the by-product of Rosa rugosa Thunb. var. plena Regal tea. BMC Complem. Altern. Med. 2018, 18, 307.
46. Huang, C.Y. Inhibition of a putative dihydropyrimidinase from Pseudomonas aeruginosa PAO1 by flavonoids and substrates of cyclic amidohydrolases. PLoS ONE 2015, 10, e0127634.
47. Bustos, P.S. Deza-Ponzio, R. Páez, P.L. Cabrera, J.L. Virgolini, M.B. Ortega, M.G. Flavonoids as protective agents against oxidative stress induced by gentamicin in systemic circulation. Potent protective activity and microbial synergism of luteolin. Food Chem. Toxicol. 2018, 118, 294–302.
48. Xie, Y. Yang, W. Tang, F. Chen, X. Ren, L. Antibacterial activities of flavonoids: Structure-activity relationship and mechanism. Curr. Med. Chem. 2015, 22, 132–149.
49. Górniak, I. Bartoszewski, R. Króliczewski, J. Comprehensive review of antimicrobial activities of plant flavonoids. Phytochem. Rev. 2019, 18, 241–272.
50. Ohemeng, K.A. Schwender, C.F. Fu, K.P.; Barrett, J.F. DNA gyrase inhibitory and antibacterial activity of some flavones. Bioorg. Med. Chem. Lett. 1993, 3, 225–230.
51. Lee, J.H. Regmi, S.C. Kim, J.A. Cho, M.H. Yun, H.; Lee, C.S. Lee, J. Apple flavonoid phloretin inhibits Escherichia coli O157:H7 biofilm formation and ameliorates colon inflammation in rats. Infect. Immun. 2011.
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