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Synthesis, In Silico and Structural Insight of Flavonol Derivative Compounds as New Competitive Dengue NS2B/NS3 Protease Inhibitor

Year 2023, Volume: 27 Issue: 3, 1157 - 1169, 28.06.2025

Abstract

This paper conducts green synthesis of silver nanoparticles using Pistacia palaestina fruit extract and studies the effects of the fabrication conditions on the size of fabricated nanoparticles during the synthesis process and the evaluation of its wound healing activity in vivo. Methods: P. palaestina extract has been used to reduce silver nitrate solution to AgNPs. The synthesized AgNPs were characterized using UV-Vis spectroscopy, Dynamic Light Scattering (DLS), Atomic Force Microscopy (AFM), and Scanning Electron Microscopy (SEM). The fabricated AgNPs were prepared as an ointment (1% w/w) and evaluated for wound healing activity using an incision wound model on rats. The time of healing was determined and compared with a positive control (gentamicin ointment 0.1%) and a negative control. Results: The fabricated AgNPs have a dark brown color, and their absorption peak was at 430 nm. The obtained particles have an average diameter of 36 nm by SEM, 55.64 nm by DLS, and 100 nm by AFM. AFM and SEM images confirmed the spherical shape of prepared AgNPs. The optimal formula for preparing AgNPs was by using fruit extract (pH 7) at a ratio of (1:9) at 35°C for 24 h. The prepared AgNPs ointment (1%) accelerated wound healing compared to a negative control group, as the time of healing was 9 ± 1.41, 12 ± 1.73, and 17 ± 2.00 days, respectively. Conclusion: It is concluded that P. palaestina extract can be utilized for fabricating AgNPs without any additions, and they have wound healing effect in experimental rats.

References

  • Aryati. Buku Ajar Demam Berdarah Dengue. Jawa Timur: Airlangga University Press. 2017. Zandi K, Teoh, BT, Sam SS, Wong PF, Mustafa M, Abubakar S. Antiviral activity of four types of bioflavonoid against dengue virus type-2. Virol J. 2011; 8: 1–11. https://doi.org/10.1186/1743-422X-8-560.
  • WHO. Update on the Dengue Situation in the Western Pasific Region. Western Pasific Region: World Health Organization. https://www.who.int (accessed on 21 June 2022)
  • Murugesan A, Manoharan M. Dengue Virus. Emerging and Reemerging Viral Pathogens. 2020:281–359. https://doi.org/10.1016%2FB978-0-12-819400-3.00016-8.
  • Mueller NH, Pattabiraman N, Ansarah-Sobrinho C, Viswanathan P, Pierson TC, Padmanabhan R. Identification and biochemical characterization of small-molecule inhibitors of west nile virus serine protease by a high-throughput screen. Antimicrob Agents Chemother. 2008;52(9):3385-3393. https://doi.org/10.1128/aac.01508-07.
  • Senthilvel P, Lavanya P, Kumar KM, Swetha R, Anitha P, Bag S, Sarveswari S, Vijayakumar V, Ramaiah S, Anbarasu A. Flavonoid from Carica papaya inhibits NS2B-NS3 protease and prevents Dengue 2 viral assembly. Bioinformation. 2013;9(18):889-895. https://doi.org/10.6026/97320630009889.
  • Chee CF, Abdullah I, Buckle MJ, Rahman NA. An Efficient Synthesis of (±)-Panduratin A and (±)-Isopanduratin A, Inhibitors of Dengue-2 Viral Activity. Tetrahedron Lett. 2010; 51(3): 495–498. https://doi.org/10.1016/j.tetlet.2009.11.030.
  • Coulerie P, Nour M, Maciuk A, Eydoux C, Guillemot JC, Lebouvier N, Hnawia E, Leblanc K, Lewin G, Canard B, Figadère B. Structure-activity relationship study of biflavonoids on the dengue virus polymerase DENV-NS5 RdRp. Planta Med. 2013; 79(14): 1313–1318. https://doi.org/10.1055/s-0033-1350672.
  • Zandi K, Teoh B-T , Sam S-S , Wong P-F, Mustafa MR, AbuBakar S. In vitro antiviral activity of fisetin, rutin and naringenin against dengue virus type-2. J Med Plants Res. 2014; 5(23): 5534-5539.
  • Habibi R, Herfindo N, Hendra R, Teruna HY Zamri A. Synthesis and molecular docking study of 1-(3- Chloropropyl)-3,5-Bis((E)-4-methoxybenzylidene)piperidin-4-one as Dengue Virus Type 2 (DEN2) NS2B/NS3 protease inhibitor candidate. Pharmacol Clin Pharm Res. 2020; 5(1): 14. https://doi.org/10.15416/pcpr.v5i1.25624.
  • Baig MH, Ahmad K, Rabbani G, Danishuddin M, Choi I. Computer aided drug design and its application to the development of potential drugs for neurodegenerative disorders. Curr Neuropharmacol. 2018; 16(6): 740-748. https://doi.org/10.2174/1570159x15666171016163510.
  • Bennett M, Burke AJ, O'Sullivan WI. Aspects of the Algar-Flynn-Oyamada (AFO) reaction. Tetrahedron. 1996; 52(20):7163-7178. https://doi.org/10.1016/0040-4020(96)00334-1.
  • Markham KR. Cara Mengidentifikasi Flavonoid. Terjemahan Kosasih Padmawinata. Bandung: Institut Teknologi Bandung 1988.
  • Coates J. Interpretation of Infrared Spectra, a Practical Approach, In: R. A. Meyers, Ed., Encyclopedia of Analytical Chemistry, John Wiley & Sons Ltd, Chichester, 2000.
  • Nandiyanto ABD, Oktiani R, Ragadhita R. How to read and interpret FTIR Spectroscope of organic material. Indones J Sci Technol. 2019; 4(1):97-118. https://doi.org/10.17509/ijost.v4i1.15806.
  • Ikhtiarudin I, Frimayanti N, Teruna HY, Zamri A. Microwave-assisted synthesis, molecular docking study and in vitro evaluation of halogen substituted flavonols against P388 murine leukemia cells. Appl Sci Technol. 2017; 1(1):375- 381.
  • Ikhtiarudin I, Agistia N, Frimayanti N, Harlianti T, Jasril J. Microwave-assisted synthesis of 1-(4-hydroxyphenyl)- 3-(4-methoxyphenyl)prop-2-en-1-one and its activities as an antioxidant, sunscreen, and antibacterial. Jurnal Kimia Sains dan Aplikasi. 2020; 23(2): 51-60. https://doi.org/10.14710/jksa.23.2.51-60.
  • Lee C, Yang W, Parr RG. Development of the Colle-Salvetticorrelationenergy formula into a functional of the electron density. Phys Rev B Condens Matter. 1988 Jan 15;37(2):785-789. https://doi.org/10.1103/physrevb.37.785.
  • Becke AD. Density-functional thermochemistry. III. The role of exact Exchange. J Chem Phys. 1993; 98, 5648–5652. https://doi.org/10.1063/1.464913.
  • Ramalingam A, Gurunathan RK, Nagarajan PC. Investigation of potential azeotrope breakers using DFT and COSMO approach. ACS Omega. 2020; 14; 5(27): 16885–16900. https://doi.org/10.1021/acsomega.0c02086.
  • Prieto-Martínez FD, Arciniega M, Medina-Franco JL. Molecular docking: Current Advance and Challanges. TIP Revista Especializa da En Ciencias Químico-Biológicas. 2018; 21:65–87. https://doi.org/10.22201/fesz.23958723e.2018.0.143.
  • Du X, Li Y, Xia YL, Ai SM, Liang J, Sang P, Ji XL, Liu SQ. Insights into Protein-Ligand Interactions: Mechanisms, Models, and Methods. Int J Mol Sci. 2016;17(2):144. https://doi.org/10.3390/ijms17020144.
  • Yamashita F, Hashida M. In silico approaches for predicting ADME properties of drugs. Drug Metab Pharmacokinet. 2004;19(5):327-338. https://doi.org/10.2133/dmpk.19.327.
  • Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001;46(1-3):3-26. https://doi.org/10.1016/s0169-409x(00)00129-0.
  • Frimayanti N, Chee CF, Zain S.M, Rahman NA. Design of new competitive dengue Ns2b/Ns3 protease inhibitors- a computational approach. Int J Mol Sci. 2011;12(2):1089-100. https://doi.org/10.3390/ijms12021089.
There are 24 citations in total.

Details

Primary Language English
Subjects Pharmaceutical Chemistry
Journal Section Articles
Authors

Neni Frimayanti

Ihsan Ikhtiarudin

Abdi Wira Septama

Adriani Susanty

Nia Daiatul Isroq

Publication Date June 28, 2025
Published in Issue Year 2023 Volume: 27 Issue: 3

Cite

APA Frimayanti, N., Ikhtiarudin, I., Septama, A. W., Susanty, A., et al. (2025). Synthesis, In Silico and Structural Insight of Flavonol Derivative Compounds as New Competitive Dengue NS2B/NS3 Protease Inhibitor. Journal of Research in Pharmacy, 27(3), 1157-1169.
AMA Frimayanti N, Ikhtiarudin I, Septama AW, Susanty A, Isroq ND. Synthesis, In Silico and Structural Insight of Flavonol Derivative Compounds as New Competitive Dengue NS2B/NS3 Protease Inhibitor. J. Res. Pharm. June 2025;27(3):1157-1169.
Chicago Frimayanti, Neni, Ihsan Ikhtiarudin, Abdi Wira Septama, Adriani Susanty, and Nia Daiatul Isroq. “Synthesis, In Silico and Structural Insight of Flavonol Derivative Compounds As New Competitive Dengue NS2B/NS3 Protease Inhibitor”. Journal of Research in Pharmacy 27, no. 3 (June 2025): 1157-69.
EndNote Frimayanti N, Ikhtiarudin I, Septama AW, Susanty A, Isroq ND (June 1, 2025) Synthesis, In Silico and Structural Insight of Flavonol Derivative Compounds as New Competitive Dengue NS2B/NS3 Protease Inhibitor. Journal of Research in Pharmacy 27 3 1157–1169.
IEEE N. Frimayanti, I. Ikhtiarudin, A. W. Septama, A. Susanty, and N. D. Isroq, “Synthesis, In Silico and Structural Insight of Flavonol Derivative Compounds as New Competitive Dengue NS2B/NS3 Protease Inhibitor”, J. Res. Pharm., vol. 27, no. 3, pp. 1157–1169, 2025.
ISNAD Frimayanti, Neni et al. “Synthesis, In Silico and Structural Insight of Flavonol Derivative Compounds As New Competitive Dengue NS2B/NS3 Protease Inhibitor”. Journal of Research in Pharmacy 27/3 (June 2025), 1157-1169.
JAMA Frimayanti N, Ikhtiarudin I, Septama AW, Susanty A, Isroq ND. Synthesis, In Silico and Structural Insight of Flavonol Derivative Compounds as New Competitive Dengue NS2B/NS3 Protease Inhibitor. J. Res. Pharm. 2025;27:1157–1169.
MLA Frimayanti, Neni et al. “Synthesis, In Silico and Structural Insight of Flavonol Derivative Compounds As New Competitive Dengue NS2B/NS3 Protease Inhibitor”. Journal of Research in Pharmacy, vol. 27, no. 3, 2025, pp. 1157-69.
Vancouver Frimayanti N, Ikhtiarudin I, Septama AW, Susanty A, Isroq ND. Synthesis, In Silico and Structural Insight of Flavonol Derivative Compounds as New Competitive Dengue NS2B/NS3 Protease Inhibitor. J. Res. Pharm. 2025;27(3):1157-69.