* Corresponding Author
Flavonoid-Capped Gold Nanoparticles from Boesenbergia rotunda: Enhanced Antioxidant Activity and Cyclin-Dependent Kinase 2 (CDK2) Inhibition via Molecular Docking
https://doi.org/10.22146/ijc.116010 Dini Nur Fauzia(1*), Afaf Baktir(2), Titik Taufikurohmah(3), Intan Permata Sari(4), Dzikra Nasyaya Mahfudhah(5), Mochamad Zakki Fahmi(6)
(1) Doctoral Program of Mathematics and Natural Sciences, Faculty of Science and Technology, Universitas Airlangga, Jl. Dr. Ir. H. Soekarno, Mulyorejo, Surabaya 60115, Indonesia; Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga, Jl. Dr. Ir. H. Soekarno, Mulyorejo, Surabaya 60115, Indonesia
(2) Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga, Jl. Dr. Ir. H. Soekarno, Mulyorejo, Surabaya 60115, Indonesia
(3) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Negeri Surabaya, Jl. Ketintang, Surabaya 60231, Indonesia
(4) Master’s Program in Chemistry, Faculty of Science and Technology, Universitas Airlangga, Jl. Dr. Ir. H. Soekarno, Mulyorejo, Surabaya 60115, Indonesia
(5) Master’s Program in Chemistry, Faculty of Science and Technology, Universitas Airlangga, Jl. Dr. Ir. H. Soekarno, Mulyorejo, Surabaya 60115, Indonesia
(6) Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga, Jl. Dr. Ir. H. Soekarno, Mulyorejo, Surabaya 60115, Indonesia
(*) Corresponding Author
Abstract
The green synthesis of gold nanoparticles (Br-AuNPs) using ethanolic extracts of Boesenbergia rotunda offers an eco-friendly approach to producing bioactive nanomaterials. This study aimed to synthesize Br-AuNPs and evaluate their antioxidant activity alongside in silico analysis of flavonoid interactions with the CDK2/cyclin A complex. The formation of Br-AuNPs was confirmed by a visible color change and a distinct SPR peak at 538–542 nm. TEM analysis revealed spherical nanoparticles with an average diameter of 14.35 ± 3.16 nm, stable for up to four months. Antioxidant activity assessed via the ABTS assay showed that Br-AuNPs exhibited significantly higher radical scavenging activity (69.01% at 120 µg/mL) compared to the crude extract (56.0%; p < 0.05). This enhancement is attributed to synergistic interactions between phytochemicals and nanoparticles, which improve surface reactivity. Furthermore, molecular docking studies were conducted to evaluate the interaction of major flavonoids from B. rotunda with the CDK2/cyclin A complex, where 6,8-di-(3,3-dimethylallyl)chrysin showed the most favorable binding affinity (−63.30 kcal/mol). These findings highlight the potential of Br-AuNPs as green-synthesized nanomaterials with enhanced antioxidant performance and provide a scientific basis for future investigations toward their development in anticancer-related applications.
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[1] Abdulateef, S.A., Raypah, M.E., Omar, A.F., Mat Jafri, M.Z., Ahmed, N.M., Mohd Kaus, N.H., Seeni, A., Mail, M.H., Tabana, Y., Ahmed, M., Al Rawashdah, S., and Barakat, K., 2023, Rapid synthesis of bovine serum albumin-conjugated gold nanoparticles using pulsed laser ablation and their anticancer activity on HeLa cells, Arabian J. Chem., 16 (11), 104395.
[2] Fahmi, M.Z., Wibowo, D.L.N., Sakti, S.C.W., Lee, H.V., and Isnaeni, I., 2020, Human serum albumin capsulated hydrophobic carbon nanodots as staining agent on HeLa tumor cell, Mater. Chem. Phys., 239, 122266.
[3] D’Angelo, N.A., Noronha, M.A., Kurnik, I.S., Câmara, M.C.C., Vieira, J.M., Abrunhosa, L., Martins, J.T., Alves, T.F.R., Tundisi, L.L., Ataide, J.A., Costa, J.S.R., Jozala, A.F., Nascimento, L.O., Mazzola, P.G., Chaud, M.V., Vicente, A.A., and Lopes, A.M., 2021, Curcumin encapsulation in nanostructures for cancer therapy: A 10-year overview, Int. J. Pharm., 604, 120534.
[4] Sengani, M., Grumezescu, A.M., and Rajeswari, V.D., 2017, Recent trends and methodologies in gold nanoparticle synthesis – A prospective review on drug delivery aspect, OpenNano, 2, 37–46.
[5] Shamloo, H.B., Jafarzadeh, S., Jouyban, A., and Soleymani, J., 2022, Synthesis and application of concanavalin A-conjugated green luminescent gold nanoparticle/fluorescent polydopamine nanoparticles for specific differentiation of cancer cells from normal cells using glycan bioreceptors, Mater. Chem. Phys., 288, 126344
[6] Badi’ah, H.I., Puspaningsih, N.N.T., Supriyanto, G., and Nasronudin, N., 2023, Rapid colorimetric sensor based on gold nanoparticles functionalized 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole for cortisol detection in saliva sample, Indones. J. Chem., 23 (4), 1009–1020.
[7] Hammami, I., Alabdallah, N.M., Al Jomaa, A., and Kamoun, M., 2021, Gold nanoparticles: Synthesis, properties and applications, J. King Saud Univ., Sci., 33, 101560.
[8] Mobaraki, M., Ghaffari, M., Zarebkohan, A., Gholipourmalekabadi, M., Fallah Omrani, V., Urbanska, A.M., and Seifalian, A., 2017, Targeted drug delivery based on gold nanoparticle derivatives, Curr. Pharm. Des., 23 (20), 2918–2929.
[9] Patil, T.P., Vibhute, A.A., Patil, S.L., Dongale, T.D., and Tiwari, A.P., 2023, Green synthesis of gold nanoparticles via Capsicum annum fruit extract: Characterization, antiangiogenic, antioxidant and anti-inflammatory activities, Appl. Surf. Sci. Adv., 13, 100372.
[10] Paiva-Santos, A.C., Herdade, A.M., Guerra, C., Peixoto, D., Pereira-Silva, M., Zeinali, M., Mascarenhas-Melo, F., Paranhos, A., and Veiga, F., 2021, Plant-mediated green synthesis of metal-based nanoparticles for dermopharmaceutical and cosmetic applications, Int. J. Pharm., 596, 120311.
[11] Elbialy, N.S., Abdelfatah, E.A., and Khalil, W.A., 2019, Antitumor activity of curcumin-green synthesized gold nanoparticles: In vitro study, BioNanoScience, 9 (4), 813–820.
[12] Kshtriya, V., Koshti, B., and Gour, N., 2021, Green synthesized nanoparticles: Classification, synthesis, characterization, and applications, Compr. Anal. Chem., 94, 173–222.
[13] Veeramani, S., Narayanan, A.P., Yuvaraj, K., Sivaramakrishnan, R., Pugazhendhi, A., Rishivarathan, I., Jose, S.P., and Ilangovan, R., 2022, Nigella sativa flavonoids surface coated gold NPs (Au-NPs) enhancing antioxidant and anti-diabetic activity, Process Biochem., 114, 193–202.
[14] Rodríguez-Arce, E., and Saldías, M., 2021, Antioxidant properties of flavonoid metal complexes and their potential inclusion in the development of novel strategies for the treatment against neurodegenerative diseases, Biomed. Pharmacother., 143, 112236.
[15] Omolaja, A.A., Pearce, B., Omoruyi, S.I., Badmus, J.A., Ismail, E., Marnewick, J., Botha, S., Benjeddou, M., Ekpo, O.E., and Hussein, A.A., 2021, The potential of chalcone-capped gold nanoparticles for the management of diabetes mellitus, Surf. Interfaces, 25, 101251.
[16] Sulaiman, G.M., Waheeb, H.M., Jabir, M.S., Khazaal, S.H., Dewir, Y.H., and Naidoo, Y., 2020, Hesperidin loaded on gold nanoparticles as a drug delivery system for a successful biocompatible, anti-cancer, anti-inflammatory and phagocytosis inducer model, Sci. Rep., 10 (1), 9362.
[17] Khan, I., Saeed, K., and Khan, I., 2019, Nanoparticles: Properties, applications and toxicities, Arabian J. Chem., 12 (7), 908–931.
[18] Kopustinskiene, D.M., Jakstas, V., Savickas, A., and Bernatoniene, J., 2020, Flavonoids as anticancer agents, Nutrients, 12 (2), 457.
[19] Christena, L.R., Subramaniam, S., Vidhyalakshmi, M., Mahadevan, V., Sivasubramanian, A., and Nagarajan, S., 2015, Dual role of pinostrobin-a flavonoid nutraceutical as an efflux pump inhibitor and antibiofilm agent to mitigate food borne pathogens, RSC Adv., 5 (76), 61881–61887.
[20] Patel, N.K., Jaiswal, G., and Bhutani, K.K., 2016, A review on biological sources, chemistry and pharmacological activities of pinostrobin, Nat. Prod. Res., 30 (18), 2017–2027.
[21] Singh, S., Meena, A., Luqman, S., and Meena, A., 2021, Acacetin and pinostrobin as a promising inhibitor of cancer-associated protein kinases, Food Chem. Toxicol., 151, 112091.
[22] Jaudan, A., Sharma, S., Abd Malek, S.N., and Dixit, A., 2018, Induction of apoptosis by pinostrobin in human cervical cancer cells: Possible mechanism of action, PLoS One, 13 (2), e0191523.
[23] Roman Junior, W.A., Gomes, D.B., Zanchet, B., Schönell, A.P., Diel, K.A.P., Banzato, T.P., Ruiz, A.L.T.G., Carvalho, J.E., Neppel, A., Barison, A., and Santos, C.A.M., 2017, Antiproliferative effects of pinostrobin and 5,6-dehydrokavain isolated from leaves of Alpinia zerumbet, Rev. Bras. Farmacogn., 27 (5), 592–598.
[24] Jadaun, A., Sharma, S., Verma, R., and Dixit, A., 2019, Pinostrobin inhibits proliferation and induces apoptosis in cancer stem-like cells through a reactive oxygen species-dependent mechanism, RSC Adv., 9 (21), 12097–12109.
[25] Sopanaporn, J., Suksawatamnuay, S., Sardikin, A., Lengwittaya, R., Chavasiri, W., Miyakawa, T., and Yompakdee, C., 2020, Pinostrobin suppresses the Ca2+-signal-dependent growth arrest in yeast by inhibiting the Swe1-mediated G2 cell-cycle regulation, FEMS Yeast Res, 20 (4), foaa026.
[26] Talib, W.H., Abuawad, A., Thiab, S., Alshweiat, A., and Mahmod, A.I., 2022, Flavonoid-based nanomedicines to target tumor microenvironment, OpenNano, 8, 100081.
[27] Khan, A.U., Dagur, H.S., Khan, M., Malik, N., Alam, M., and Mushtaque, M., 2021, Therapeutic role of flavonoids and flavones in cancer prevention: Current trends and future perspectives, Eur. J. Med. Chem. Rep., 3, 100010.
[28] Muniyappan, N., Pandeeswaran, M., and Amalraj, A., 2021, Green synthesis of gold nanoparticles using Curcuma pseudomontana isolated curcumin: Its characterization, antimicrobial, antioxidant and anti-inflammatory activities, Environ. Chem. Ecotoxicol., 3, 117–124.
[29] Cirillo, G., Curcio, M., Vittorio, O., Iemma, F., Restuccia, D., Spizzirri, U.G., Puoci, F., and Picci, N., 2016, Polyphenol conjugates and human health: A perspective review, Crit. Rev. Food Sci. Nutr., 56 (2), 326–337.
[30] Brown, S.D., Nativo, P., Smith, J.A., Stirling, D., Edwards, P.R., Venugopal, B., Flint, D.J., Plumb, J.A., Graham, D., and Wheate, N.J., 2010, Gold nanoparticles for the improved anticancer drug delivery of the active component of oxaliplatin, J. Am. Chem. Soc., 132 (13), 4678–4684.
[31] Oueslati, M.H., Ben Tahar, L., and Harrath, A.H., 2020, Catalytic, antioxidant and anticancer activities of gold nanoparticles synthesized by kaempferol glucoside from Lotus leguminosae, Arabian J. Chem., 13 (1), 3112–3122.
[32] Kumar, S., and Pandey, A.K., 2013, Chemistry and biological activities of flavonoids: An overview, Sci. World J., 2013 (1), 162750.
[33] Amawi, H., Ashby, C.R., and Tiwari, A.K., 2017, Cancer chemoprevention through dietary flavonoids: What’s limiting?, Chin. J. Cancer, 36 (1), 50.
[34] Mir, S.A., Dar, A., Hamid, L., Nisar, N., Malik, J.A., Ali, T., and Bader, G.N., 2024, Flavonoids as promising molecules in the cancer therapy: An insight, Curr. Res. Pharmacol. Drug Discovery, 6, 100167.
[35] Solanki, P., Sarwadia, S., Athar, M., Jha, P.C., and Manhas, A., 2024, Targeting the cyclin-dependent kinase family in anticancer drug discovery: From computational to experimental studies, Chem. Phys. Impact, 9, 100768.
[36] Tadesse, S., Anshabo, A.T., Portman, N., Lim, E., Tilley, W., Caldon, C.E., and Wang, S., 2020, Targeting CDK2 in cancer: Challenges and opportunities for therapy, Drug Discovery Today, 25 (2), 406–413.
[37] Zhang, J., Gan, Y., Li, H., Yin, J., He, X., Lin, L., Xu, S., Fang, Z., Kim, B., Gao, L., Ding, L., Zhang, E., Ma, X., Li, J., Li, L., Xu, Y., Horne, D., Xu, R., Yu, H., Gu, Y., and Huang, W., 2022, Inhibition of the CDK2 and Cyclin A complex leads to autophagic degradation of CDK2 in cancer cells, Nat. Commun., 13 (1), 2835.
[38] Ali Chohan, T., Qian, H., Pan, Y., and Chen, J.Z., 2015, Cyclin-dependent kinase-2 as a target for cancer therapy: Progress in the development of CDK2 inhibitors as anti-cancer agents, Curr. Med. Chem., 22 (2), 237–263.
[39] Kwon, S., Bae, H., Jo, J., and Yoon, S., 2019, Comprehensive ensemble in QSAR prediction for drug discovery, BMC Bioinf., 20 (1), 521.
[40] Radini, I.A.M., Ibrahim, D.A., and Khidre, R.E., 2019, Design, synthesis and biological estimation of innovative pyrazoles as anticancer agents targeting CDK2, Acta Pol. Pharm., 76 (3), 453–468.
[41] Xing, F., Wang, Z., Bahadar, N., Wang, C., and Wang, X.D., 2024, Molecular insights into kaempferol derivatives as potential inhibitors for CDK2 in colon cancer: Pharmacophore modeling, docking, and dynamic analysis, Front. Chem., 12, 1440196.
[42] Stringhetta, G.R., Mass, E.B., Faria Gomes, I.N., Fonseca Peixoto, M.C., Tejada, A.H., Susucchi, L., Alves Bezerra, A.J., Silva Resende, P.V., Vendrúsculo, V., Reis, R.M., Russowsky, D., and Oliveira, R.J.D.S., 2025, Design, synthesis and evaluation of quinazoline-chalcone hybrids as inducers of cell-cycle arrest and apoptosis in breast cancer via DNA damage and CDK2/ATR inhibition, Eur. J. Med. Chem. Rep., 13, 100250.
[43] Rahman, S., Talukdar, N.C., Patowary, K., and Mohanta, Y.K., 2024, Propolis from the North-East region of India exhibits potent antioxidant and anticancer activity against breast cancer cells, Biocatal. Agric. Biotechnol., 59, 103269.
[44] Liu, J.Z., Lyu, H.C., Fu, Y.J., Jiang, J.C., and Cui, Q., 2022, Simultaneous extraction of natural organic acid and flavonoid antioxidants from Hibiscus manihot L. flower by tailor-made deep eutectic solvent, LWT-Food Sci. Technol., 163, 113533.
[45] Kanchanapiboon, J., Kongsa, U., Pattamadilok, D., Kamponchaidet, S., Wachisunthon, D., Poonsatha, S., and Tuntoaw, S., 2020, Boesenbergia rotunda extract inhibits Candida albicans biofilm formation by pinostrobin and pinocembrin, J. Ethnopharmacol., 261, 113193.
[46] Vemuri, S.K., Banala, R.R., Mukherjee, S., Uppula, P., Subbaiah, G.P.V., Gurava Reddy, A.V., and Malarvilli, T., 2019, Novel biosynthesized gold nanoparticles as anti-cancer agents against breast cancer: Synthesis, biological evaluation, molecular modelling studies, Mater. Sci. Eng., C, 99, 417–429.
[47] Hanwell, M.D., Curtis, D.E., Lonie, D.C., Vandermeersch, T., Zurek, E., and Hutchison, G.R., 2012, Avogadro: An advanced semantic chemical editor, visualization, and analysis platform, J. Cheminf., 4 (1), 17.
[48] Allen, W.J., Balius, T.E., Mukherjee, S., Brozell, S.R., Moustakas, D.T., Lang, P.T., Case, D.A., Kuntz, I.D., and Rizzo, R.C., 2015, DOCK 6: Impact of new features and current docking performance, J. Comput. Chem., 36 (15), 1132–1156.
[49] Diedrich, K., Krause, B., Berg, O., and Rarey, M., 2023, PoseEdit: Enhanced ligand binding mode communication by interactive 2D diagrams, J. Comput.-Aided Mol. Des., 37 (10), 491–503.
[50] Hidayati, M.D., Ersam, T., Shimizu, K., and Fatmawati, S., 2017, Antioxidant activity of Syzygium polyanthum extracts, Indones. J. Chem., 17 (1), 49–53.
[51] Sindhu, K., Rajaram, A., Sreeram, K.J., and Rajaram, R., 2014, Curcumin conjugated gold nanoparticle synthesis and its biocompatibility, RSC Adv., 4 (4), 1808–1818.
[52] Al Shehab, S., El Kurdi, R., and Patra, D., 2020, Curcumin mediated PEG thiol acid conjugated gold nanoparticles for the determination of melamine, Microchem. J., 153, 104382.
[53] Shaabani, E., Amini, S.M., Kharrazi, S., and Tajerian, R., 2017, Curcumin coated gold nanoparticles: Synthesis, characterization, cytotoxicity, antioxidant activity and its comparison with citrate coated gold nanoparticles, Nanomed. J., 4 (2), 115–125.
[54] Hosny, M., Eltaweil, A.S., Mostafa, M., El-Badry, Y.A., Hussein, E.E., Omer, A.M., and Fawzy, M., 2022, Facile synthesis of gold nanoparticles for anticancer, antioxidant applications, and photocatalytic degradation of toxic organic pollutants, ACS Omega, 7 (3), 3121–3133.
[55] Merugu, R., and Gothalwal, R., 2021, Microscopic techniques for characterisation of nanomaterials: A minireview, Mater. Today: Proc., 46, 4753–4757.
[56] Augustine, R., Hasan, A., Primavera, R., Wilson, R.J., Thakor, A.S., and Kevadiya, B.D., 2020, Cellular uptake and retention of nanoparticles: Insights on particle properties and interaction with cellular components, Mater. Today Commun., 25, 101692.
[57] Percoco, R.M., Schirinzi, S., Mandriota, G., Cortese, B., Gigli, G., Palamà, I.E., and Maiorano, G., 2025, Smart inorganic nanoparticles in nanomedicine: Strategies for synthesis and functionalization, Int. J. Pharm., 634, 126192.
[58] Nizamov, S., Sazdovska, S.D., and Mirsky, V.M., 2022, A review of optical methods for ultrasensitive detection and characterization of nanoparticles in liquid media with a focus on the wide field surface plasmon microscopy, Anal. Chim. Acta, 1202, 339633.
[59] Mahmoudi, A., Kesharwani, P., Majeed, M., Teng, Y., and Sahebkar, A., 2022, Recent advances in nanogold as a promising nanocarrier for curcumin delivery, Colloids Surf., B, 215, 112481.
[60] McCarron, E., and Chambers, G., 2021, A review of suitable analytical technology for physio-chemical characterisation of nanomaterials in the customs laboratory, Talanta Open, 4, 100069.
[61] Muharrami, L.K., Santoso, M., and Fatmawati, S., 2024, Chemical profiles, in silico pharmacokinetic and toxicity prediction of bioactive compounds from Boesenbergia rotunda, Case Stud. Chem. Environ. Eng., 10, 100992.
[62] Rokkarukala, S., Cherian, T., Ragavendran, C., Mohanraju, R., Kamaraj, C., Almoshari, Y., Albariqi, A., Sultan, M.H., Alsalhi, A., and Mohan, S., 2023, One-pot green synthesis of gold nanoparticles using Sarcophyton crassocaule, a marine soft coral: Assessing biological potentialities of antibacterial, antioxidant, anti-diabetic and catalytic degradation of toxic organic pollutants, Heliyon, 9 (3), e14668.
[63] Sanna, V., Pala, N., DessÌ, G., Manconi, P., Mariani, A., Dedola, S., Rassu, M., Crosio, C., Iaccarino, C., and Sechi, M., 2014, Single-step green synthesis and characterization of gold-conjugated polyphenol nanoparticles with antioxidant and biological activities, Int. J. Nanomed., 9 (1), 4935–4951.
[64] Malumbres, M., and Barbacid, M., 2009, Cell cycle, CDKs and cancer: A changing paradigm, Nat. Rev. Cancer, 9 (3), 153–166.
DOI: https://doi.org/10.22146/ijc.116010
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