Emodin Alcohols: Design, Synthesis, Biological Evaluation and Multitargeting Studies with DNA, RNA, and HSA


Дәйексөз келтіру

Толық мәтін

Аннотация

Objective:A series of novel emodin alcohols were designed and prepared in an effort to overcome the increasing microorganism resistance.

Methods:Novel emodin alcohols were prepared from commercial emodin and different nitrogen-containing heterocycles via different synthetic strategies, such as O-alkylation and N-alkylation. The antimicrobial activity of synthesized emodin compounds was evaluated in vitro by a two-fold serial dilution technique. The interaction of emodin compound 3d with biomolecule was researched using UV-vis spectroscopic method and fluorescence spectroscopy.

Results:Emodin compound 3d containing 2-methyl-5-nitro imidazole ring showed relatively good antimicrobial activity. Notably, it exhibited equivalent activity against S. aureus in comparison to the reference drug norfloxacin (MIC = 4 µg/mL). The combination of strong active compound 3d with reference drugs showed better antimicrobial activity with less dosage and a broader antimicrobial spectrum than their separate use. Further research displayed that emodin compound 3d could intercalate into S. aureus DNA to form the 3d–DNA complex, which might correlate with the inhibitory activity. The hydrogen bonds were found between S. aureus DNA gyrase and strong active compound 3d during the docking research, which were in accordance with the spectral experiment results. The interaction with yeast RNA of compound 3d could also form a complex via hydrogen bonds. The hydrogen bonds were found to play a major role in the transportation of emodin compound 3d by human serum albumin (HSA), as confirmed by molecular simulation.

Conclusion:This work provides a promising starting point to optimize the structures of emodin derivatives as potent antimicrobial agents.

Авторлар туралы

Hai-Guang Wang

School of Pharmacy, Linyi University

Email: info@benthamscience.net

Hui-Zhen Zhang

School of Pharmacy, Linyi University

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Әдебиет тізімі

  1. Zhong, C.; Zhang, F.; Zhu, N.; Zhu, Y.; Yao, J.; Gou, S.; Xie, J.; Ni, J. Ultra-short lipopeptides against gram-positive bacteria while alleviating antimicrobial resistance. Eur. J. Med. Chem., 2021, 212, 113138. doi: 10.1016/j.ejmech.2020.113138 PMID: 33422980
  2. Dighe, S.N.; Collet, T.A. Recent advances in DNA gyrase-targeted antimicrobial agents. Eur. J. Med. Chem., 2020, 199, 112326. doi: 10.1016/j.ejmech.2020.112326 PMID: 32460040
  3. Chalothorn, T.; Rukachaisirikul, V.; Phongpaichit, S.; Pannara, S.; Tansakul, C. Synthesis and antibacterial activity of emodin and its derivatives against methicillin-resistant Staphylococcus aureus. Tetrahedron Lett., 2019, 60(35), 151004. doi: 10.1016/j.tetlet.2019.151004
  4. Semwal, R.B.; Semwal, D.K.; Combrinck, S.; Viljoen, A. Emodin - A natural anthraquinone derivative with diverse pharmacological activities. Phytochemistry, 2021, 190, 112854. doi: 10.1016/j.phytochem.2021.112854 PMID: 34311280
  5. Kim, H.; Jang, J.H.; Kim, S.C.; Cho, J.H. Development of a novel hybrid antimicrobial peptide for targeted killing of Pseudomonas aeruginosa. Eur. J. Med. Chem., 2020, 185, 111814. doi: 10.1016/j.ejmech.2019.111814 PMID: 31678742
  6. Luo, N.; Fang, J.; Wei, L.; Sahebkar, A.; Little, P.J.; Xu, S.; Luo, C.; Li, G. Emodin in atherosclerosis prevention: Pharmacological actions and therapeutic potential. Eur. J. Pharmacol., 2021, 890, 173617. doi: 10.1016/j.ejphar.2020.173617 PMID: 33010303
  7. Duan, F.; Li, X.; Cai, S.; Xin, G.; Wang, Y.; Du, D.; He, S.; Huang, B.; Guo, X.; Zhao, H.; Zhang, R.; Ma, L.; Liu, Y.; Du, Q.; Wei, Z.; Xing, Z.; Liang, Y.; Wu, X.; Fan, C.; Ji, C.; Zeng, D.; Chen, Q.; He, Y.; Liu, X.; Huang, W. Haloemodin as novel antibacterial agent inhibiting DNA gyrase and bacterial topoisomerase I. J. Med. Chem., 2014, 57(9), 3707-3714. doi: 10.1021/jm401685f PMID: 24588790
  8. Lu, C.; Wang, H.; Lv, W.; Xu, P.; Zhu, J.; Xie, J.; Liu, B.; Lou, Z. Antibacterial properties of anthraquinones extracted from rhubarb against Aeromonas hydrophila. Fish. Sci., 2011, 77(3), 375-384. doi: 10.1007/s12562-011-0341-z
  9. Zhang, H.Z.; Damu, G.L.V.; Cai, G.X.; Zhou, C.H. Design, synthesis and antimicrobial evaluation of novel benzimidazole type of Fluconazole analogues and their synergistic effects with Chloromycin, Norfloxacin and Fluconazole. Eur. J. Med. Chem., 2013, 64, 329-344. doi: 10.1016/j.ejmech.2013.03.049 PMID: 23644216
  10. Emami, S.; Ghobadi, E.; Saednia, S.; Hashemi, S.M. Current advances of triazole alcohols derived from fluconazole: Design, in vitro and in silico studies. Eur. J. Med. Chem., 2019, 170, 173-194. doi: 10.1016/j.ejmech.2019.03.020 PMID: 30897396
  11. Zhang, H.Z.; Gan, L.L.; Wang, H.; Zhou, C.H. New progress in azole compounds as antimicrobial agents. Mini Rev. Med. Chem., 2016, 17(2), 122-166. doi: 10.2174/1389557516666160630120725 PMID: 27484625
  12. Zhang, H.Z.; Zhao, Z.L.; Zhou, C.H. Recent advance in oxazole-based medicinal chemistry. Eur. J. Med. Chem., 2018, 144, 444-492. doi: 10.1016/j.ejmech.2017.12.044 PMID: 29288945
  13. Tan, J.H.; Zhang, Q.X.; Huang, Z.S.; Chen, Y.; Wang, X.D.; Gu, L.Q.; Wu, J.Y. Synthesis, DNA binding and cytotoxicity of new pyrazole emodin derivatives. Eur. J. Med. Chem., 2006, 41(9), 1041-1047. doi: 10.1016/j.ejmech.2006.04.006 PMID: 16716458
  14. Zhang, H-Z.; Ning, Z-W.; Zhou, C.H. Design, synthesis and antimicrobial evaluation of novel benzimidazole incorporated naphthalimide derivatives as Salmonella typhimurium DNA intercalators, and combination researches. Med. Chem., 2022, 18(5), 544-557. doi: 10.2174/1573406417666210712105922 PMID: 34254924
  15. Zhang, H.Z.; He, S.C.; Peng, Y.J.; Zhang, H.J.; Gopala, L.; Tangadanchu, V.K.R.; Gan, L.L.; Zhou, C.H. Design, synthesis and antimicrobial evaluation of novel benzimidazole-incorporated sulfonamide analogues. Eur. J. Med. Chem., 2017, 136, 165-183. doi: 10.1016/j.ejmech.2017.04.077 PMID: 28494254
  16. He, S.C.; Zhang, H.Z.; Zhang, H.J.; Sun, Q.; Zhou, C.H. Design and synthesis of novel sulfonamide-derived triazoles and bioactivity exploration. Med. Chem., 2020, 16(1), 104-118. doi: 10.2174/1573406414666181106124852 PMID: 30398118
  17. Jeyakkumar, P.; Zhang, L.; Avula, S.R.; Zhou, C.H. Design, synthesis and biological evaluation of berberine-benzimidazole hybrids as new type of potentially DNA-targeting antimicrobial agents. Eur. J. Med. Chem., 2016, 122, 205-215. doi: 10.1016/j.ejmech.2016.06.031 PMID: 27371924
  18. Yin, B.T.; Yan, C.Y.; Peng, X.M.; Zhang, S.L.; Rasheed, S.; Geng, R.X.; Zhou, C.H. Synthesis and biological evaluation of α-triazolyl chalcones as a new type of potential antimicrobial agents and their interaction with calf thymus DNA and human serum albumin. Eur. J. Med. Chem., 2014, 71, 148-159. doi: 10.1016/j.ejmech.2013.11.003 PMID: 24291568
  19. Wang, X.P.; Xu, W.F. Chemical synthesis and antitumor activities of emodin derivatives. Zhongguo Yaowu Huaxue Zazhi, 2005, 15, 321-326.
  20. National Committee for Clinical Laboratory Standards Approved standard Document; National Committee for Clinical Laboratory Standards: Wayne, PA, 2002, p. M27-A2.
  21. Kitahara, T.; Aoyama, Y.; Hirakata, Y.; Kamihira, S.; Kohno, S.; Ichikawa, N.; Nakashima, M.; Sasaki, H.; Higuchi, S. In vitro activity of lauric acid or myristylamine in combination with six antimicrobial agents against methicillin-resistant Staphylococcus aureus (MRSA). Int. J. Antimicrob. Agents, 2006, 27(1), 51-57. doi: 10.1016/j.ijantimicag.2005.08.020 PMID: 16318911
  22. Wang, L.L.; Battini, N.; Bheemanaboina, R.R.Y.; Ansari, M.F.; Chen, J.P.; Xie, Y.P.; Cai, G.X.; Zhang, S.L.; Zhou, C.H. A new exploration towards aminothiazolquinolone oximes as potentially multi-targeting antibacterial agents: Design, synthesis and evaluation acting on microbes, DNA, HSA and topoisomerase IV. Eur. J. Med. Chem., 2019, 179, 166-181. doi: 10.1016/j.ejmech.2019.06.046 PMID: 31254919
  23. Zhang, Y.; Tangadanchu, V.K.R.; Cheng, Y.; Yang, R.G.; Lin, J.M.; Zhou, C.H. Potential antimicrobial isopropanol-conjugated carbazole azoles as dual targeting inhibitors of Enterococcus faecalis. ACS Med. Chem. Lett., 2018, 9(3), 244-249. doi: 10.1021/acsmedchemlett.7b00514 PMID: 29541368
  24. Cui, S.F.; Peng, L.P.; Zhang, H.Z.; Rasheed, S.; Vijaya Kumar, K.; Zhou, C.H. Novel hybrids of metronidazole and quinolones: Synthesis, bioactive evaluation, cytotoxicity, preliminary antimicrobial mechanism and effect of metal ions on their transportation by human serum albumin. Eur. J. Med. Chem., 2014, 86, 318-334. doi: 10.1016/j.ejmech.2014.08.063 PMID: 25173851
  25. Li, X.L.; Hu, Y.J.; Wang, H.; Yu, B.Q.; Yue, H.L. Molecular spectroscopy evidence of berberine binding to DNA: Comparative binding and thermodynamic profile of intercalation. Biomacromolecules, 2012, 13(3), 873-880. doi: 10.1021/bm2017959 PMID: 22316074
  26. Zhang, G.; Fu, P.; Wang, L.; Hu, M. Molecular spectroscopic studies of farrerol interaction with calf thymus DNA. J. Agric. Food Chem., 2011, 59(16), 8944-8952. doi: 10.1021/jf2019006 PMID: 21761894
  27. Cui, S.F.; Addla, D.; Zhou, C.H. Novel 3-aminothiazolquinolones: Design, synthesis, bioactive evaluation, SARs, and preliminary antibacterial mechanism. J. Med. Chem., 2016, 59(10), 4488-4510. doi: 10.1021/acs.jmedchem.5b01678 PMID: 27115717
  28. Wang, L.L.; Battini, N.; Bheemanaboina, R.R.Y.; Zhang, S.L.; Zhou, C.H. Design and synthesis of aminothiazolyl norfloxacin analogues as potential antimicrobial agents and their biological evaluation. Eur. J. Med. Chem., 2019, 167, 105-123. doi: 10.1016/j.ejmech.2019.01.072 PMID: 30769240
  29. Xu, H.; Deng, H.; Zhang, Q.L.; Huang, Y.; Liu, J.Z.; Ji, L.N. Synthesis and spectroscopic RNA binding studies of Ru(phen)2MHPIP2+. Inorg. Chem. Commun., 2003, 6(6), 766-768. doi: 10.1016/S1387-7003(03)00079-0
  30. Suryawanshi, V.D.; Anbhule, P.V.; Gore, A.H.; Patil, S.R.; Kolekar, G.B. Spectroscopic investigation on the interaction of pyrimidine derivative, 2-amino-6-hydroxy-4- (3,4-dimethoxyphenyl)-pyrimidine-5-carbonitrile with human serum albumin: Mechanistic and conformational study. Ind. Eng. Chem. Res., 2012, 51(1), 95-102. doi: 10.1021/ie202005c
  31. Ibrahim, N.; Ibrahim, H.; Kim, S.; Nallet, J.P.; Nepveu, F. Interactions between antimalarial indolone-N-oxide derivatives and human serum albumin. Biomacromolecules, 2010, 11(12), 3341-3351. doi: 10.1021/bm100814n PMID: 21080702
  32. Hu, Y.J.; Liu, Y.; Xiao, X.H. Investigation of the interaction between Berberine and human serum albumin. Biomacromolecules, 2009, 10(3), 517-521. doi: 10.1021/bm801120k PMID: 19173654
  33. Lakowicz, J.R. Principles of Fluorescence Spectroscopy, 3rd ed; Springer: New York, 2006. doi: 10.1007/978-0-387-46312-4
  34. Zhang, S.L.; Damu, G.L.V.; Zhang, L.; Geng, R.X.; Zhou, C.H. Synthesis and biological evaluation of novel benzimidazole derivatives and their binding behavior with bovine serum albumin. Eur. J. Med. Chem., 2012, 55, 164-175. doi: 10.1016/j.ejmech.2012.07.015 PMID: 22863183
  35. Zhang, S.L.; Chang, J.J.; Damu, G.L.V.; Geng, R.X.; Zhou, C.H. Berberine azoles as antimicrobial agents: Synthesis, biological evaluation and their interactions with human serum albumin. Med. Chem. Comm., 2013, 4(5), 839-846. doi: 10.1039/c3md00032j
  36. Mote, U.S.; Patil, S.R.; Bhosale, S.H.; Han, S.H.; Kolekar, G.B. Fluorescence resonance energy transfer from tryptophan to folic acid in micellar media and deionised water. J. Photochem. Photobiol. B, 2011, 103(1), 16-21. doi: 10.1016/j.jphotobiol.2011.01.006 PMID: 21288734
  37. Zhang, S.L.; Chang, J.J.; Damu, G.L.V.; Fang, B.; Zhou, X.D.; Geng, R.X.; Zhou, C.H. Novel berberine triazoles: Synthesis, antimicrobial evaluation and competitive interactions with metal ions to Human Serum Albumin. Bioorg. Med. Chem. Lett., 2013, 23(4), 1008-1012. doi: 10.1016/j.bmcl.2012.12.036 PMID: 23312473
  38. Lv, J.S.; Peng, X.M.; Kishore, B.; Zhou, C.H. 1,2,3-Triazole-derived naphthalimides as a novel type of potential antimicrobial agents: Synthesis, antimicrobial activity, interaction with calf thymus DNA and human serum albumin. Bioorg. Med. Chem. Lett., 2014, 24(1), 308-313. doi: 10.1016/j.bmcl.2013.11.013 PMID: 24295786

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