Synthesis and High Antioxidant Activity of C-Alkyl Calix[4]resorcinarene and C-Alkyl Calix[4]pyrogallolarene Derivatives
Keywords:
Antioxidant, Alkyl Chain, Calix[4]resorcinarene, Calix[4]pyrogallolarene, In Vitro
Abstract
In the present work, we reported a successful synthesis and high antioxidant activity of C-alkylcalix[4]resorcinarene and C-alkylcalix[4]pyrogallolarene derivatives. The C-alkylcalix[4]resorcinarenes were prepared from a cyclization reaction of resorcinol and either pentanaldehyde or octanaldehyde in acidic condition. Meanwhile, the C-alkylcalix[4]pyrogallolarenes were prepared from a cyclization reaction of pyrogallol with pentanaldehyde or octanaldehyde. Four synthesized products, i.e. nBu-CR, nHep-CR, nBu-CP, and nHep-CP, were successfully prepared in 92.4-96.4% yield. The chemical structure of these products was elucidated by Fourier transform infrared (FTIR), liquid chromatography-mass spectrometry (LC-MS), and proton nuclear magnetic resonance (1H-NMR) analysis. The antioxidant activity assay of these compounds was evaluated through an in vitro assay employing 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. From the DPPH assay, it was found that the half-maximal inhibitory concentration (IC50) values of nBu-CR, nHep-CR, nBu-CP, and nHep-CP compounds were 25.1, 22.9, 11.5, and 21.9 µg mL-1, respectively. The IC50 value of the synthesized compounds was 2.0-4.3 times lower than the IC50 value of butylated hydroxytoluene (BHT) as the positive standard (49.9 µg mL-1), which is remarkable. This finding demonstrates that either C-alkylcalix[4]resorcinarenes or C-alkylcalix[4]pyrogallolarenes are better antioxidant agents than BHT. The nHep-CR compound was found as the best antioxidant agent from the other compounds due to weaker intramolecular and intermolecular hydrogen bonding as well as longer alkyl chain.
References
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Asirvatham R, Akhil J. 2017. Evaluation of in vitro and in vivo anti-oxidant potential of Morinda reticulata gamble tubers in Wistar albino rats subjected to CCl4 and paracetamol induced hepatotoxicity. Indonesian J. Pharm. 28: 147-157. doi: 10.14499/indonesianjpharm28iss3pp147
Chandra P, Sharma RK, Arora DS. 2020. Antioxidant compounds from microbial sources: a review. Food Res. Int. 129: 108849. doi: 10.1016/j.foodres.2019.108849
Christhudas IN, Kumar PP, Agastian P. 2013. In vitro a-glucosidase inhibition and antioxidative potential of an endophyte species (Streptomyces sp. Loyola UGC) isolated from Datura stramonium L. Curr. Microbiol. 67: 69-76. doi: 10.1007/s00284-013-0329-2
Dewi EU, Nursalam N, Mahmudah M, Halawa A, Ayu A. 2020. Factors affecting hardiness in cancer patients: a case study of the Indonesian cancer foundation. J. Public Health Res. 9: 1807. doi: 10.4081/jphr.2020.1819.
Fidrianny I, Hartati R, Raveendaran N. 2012. Antioxidant activity of ethyl acetate extract of red Psidium guajava L. leaves grown in Manoko, Lembang - Indonesia. Indonesian J. Pharm. 23: 36-40. doi: 10.14499/indonesianjpharm23iss1pp36-40
Gubaidullin AT, Nikolaeva IL, Kharitonov DI, Litvinov IA, Bashmakova NI, Burilov AR, Pudovik MA, Konovalov AI. 2000. Effect of substituents on the supramolecular structure and stability of crystals of dialkylaminomethylated calix[4]resorcinolarenes. Russian J. Gen. Chem. 72: 259-267. doi: 10.1023/A:1015481804340
Govindappa M, Bharath N, Shruthi HB, Santoyo G. 2011. In vitro antioxidant activity and phytochemical screening of endophytic extracts of Crotalaria pallida. Free Radic. Antioxidants. 1: 79-86. doi: 10.5530/ax.2011.3.11
Handayani SN, Jumina, Mustofa, Swasono RT. 2016. Antioxidant assay of C-2-hydroxyphenylcalix[4]resorcinarene using DPPH method. Int. J. ChemTech Res. 9: 278-283.
Handayani SN, Ekowati H, Irmanto, Aprilia DNA, Utami S. 2020. Synthesis of phenylcalix[4]resorcinarene sulfonate and its application as an antioxidant. AIP Conf. Proc. 2237: 020067. doi: 10.1063/5.0006139
Jumina, Siswanta D, Zulkarnain AK, Triono S, Priatmoko, Yuanita E, Imawan AC, Fatmasari N, Nursalim I. 2019. Development of C-arylcalix[4]resorcinarenes and C-arylcalix[4]pyrogallolarenes as antioxidants and UV-B protector. Indones. J. Chem. 19: 273-284. doi: 10.22146/ijc.26868
Jumina, Priastomo Y, Setiawan HR, Mutmainah, Kurniawan YS, Ohto K. 2020a. Simultaneous removal of lead(II), chromium(III) and copper(II) heavy metal ions through an adsorption process using C-phenylcalix[4]pyrogallolarene material. J. Environ. Chem. Eng. 8: 103971. doi: 10.1016/j.jece.2020.103971
Jumina, Setiawan HR, Triono S, Kurniawan YS, Siswanta D, Zulkarnain AK, Kumar N. 2020b. The C-arylcalix[4]pyrogallolarene sulfonic acid: a novel and efficient organocatalyst material for biodiesel production. Bull. Chem. Soc. Jpn. 93: 252-259. doi: 10.1246/bcsj.20190275
Jumina, Amalina I, Triono S, Kurniawan YS, Priastomo Y, Ohto K, Yamin BM. 2021. Preliminary application of organocatalyst based on C-arylcalix[4]-2-methylresorcinarenes sulfonic acid material derived from Indonesian natural products for biodiesel production. Bull. Korean Chem. Soc. doi: 10.1002/bkcs.12194
Kementerian Kesehatan RI. 2018. Hasil utama Riskedas 2018. Retrieved from https://www.litbang.kemkes.go.id/hasil-utama-riskesdas-2018/
Keypour H, Rezaei MT, Jamshidi M, Farida SHM, Karamian R. 2021. Synthesis, cytotoxicity, and antioxidant activity by in vitro and molecular docking studies of an asymmetrical diamine containing piperazine moiety and related Zn(II), Cd(II) and Mn(II) macrocyclic Schiff base complexes. Inorg. Chem. Commun. 125: 108443. doi: 10.1016/j.inoche.2021.108443
Lukitaningsih E, Holzgrabe U. 2014. Bioactive compounds in benkoang (Pachyrhizus erosus) as antioxidant and Tyrosinase inhibiting agents. Indonesian J. Pharm. 25: 68-75. doi: 10.14499/indonesianjpharm25iss2pp75
Malik I, Stanzel L, Csollei J, Curillova J. 2017. The in vitro antioxidant properties of 2-alkoxyphenylcarbamic acid derivatives containing a 4'-(substituted phenyl)piperazin-1'-yl moiety determined by the 2,2'-azinobis(3-ethyl-benzothiazoline-6-sulfonic acid) derived radical cation (ABTS) and ferric reducing antioxidant power (FRAP) assays. Indonesian J. Pharm. 28: 1-9. doi: 10.14499/indonesianjpharm28iss1pp1
Martiningsih, Haris A. 2019. Risiko penyakit kardiovaskuler pada peserta program pengelolaan penyakit kronis (PROLANIS) di puskesmas kota Bima: Korelasinya dengan ankle brachial index dan obesitas. Jurnal Keperawatan Indonesia 22: 200-208. doi: 10.7454/jki.v22i3.880
Masduqi AF, Franyoto YD, Kusmita L, Muchlisin S, Widyananto PA, Sulistyani, Wijayanti DP. 2020. Antioxidant activity on pigments of bacterial symbionts of soft coral from Jepara sea. Indones. J. Nat. Pigm. 2: 43-47. doi: 10.33479/ijnp.2020.02.2.43
Neha K, Haider MR, Pathak A, Yar MS. 2019. Medicinal prospects of antioxidants: a review. Eur. J. Med. Chem. 178: 687-704. doi: 10.1016/j.ejmech.2019.06.010
Ngurah BIGM. 2018. Synthetic C-methoxyphenylcalix[4]resorcinarene and its antioxidant activity. J. Appl. Chem. Sci. 5: 403-408. doi: 10.22341/jacs.on.00501p403
Pringgenies D, Idris R. 2019. The antioxidant activity of carotenoid pigments in the bacterial symbionts of seagrass Syringodium isoetifolium. Indones. J. Nat. Pigm. 1: 12-15. doi: 10.33479/ijnp.2019.01.1.12
Priyangga KTA, Kurniawan YS, Yuliati L. 2020. Synthesis and characterizations of C-3-nitrophenylcalix[4]resorcinarene as a potential chemosensor for La(III) ions. IOP Conf. Ser.: Mater. Sci. Eng. 959: 012014. doi: 10.1088/1757-899X/959/1/012014
Purnomo TAB, Yuliati L. 2020. High antioxidant activity of pucuk merah (Syzygium oleina) leaf and zinnia (Zinnia elegans) flower extracts. Indones. J. Nat. Pigm. 2: 54-58. doi: 10.33479/ijnp.2020.02.2.54
Shahidi F, Ambigaipalan P. 2015. Phenolics and polyphenolics in foods, beverages and spices: antioxidant activity and health effects: a review. J. Funct. Foods 18: 820-897. doi: 10.1016/j.jff.2015.06.018
Toghueo RMK, Boyom FF. 2019. Endophytes from etno-pharmacological plants: Sources of novel antioxidants: a systematic review. Biocatal. Agric. Biotechnol. 22: 101430. doi: 10.1016/j.bcab.2019.101430
Valand NN, Patel MB, Menon SK. 2015. Curcumin-p-sulfonatocalix[4]resorcinarene (p-SC[4]R) interaction: thermo-physico chemistry, stability and biological evaluation. RSC Adv. 5: 8739-8752. doi: 10.1039/C4RA12047G
Vasundhara M, Baranwal M, Kumar A. 2016. Fusarium tricinctum, an endophytic fungus exhibits cell growth inhibition and antioxidant activity. Indian J. Microbiol. 56: 433-438. doi: 10.1007/s12088-016-0600-x
Venkatachalam H, Yogendra N, Jayashree BS. 2012. Synthesis, characterization and antioxidant activities of synthetic chalcones and flavones. APCBEE Procedia 3: 2019-213. doi: 10.1016/j.apcbee.2012.06.071
Zhong K, Gao X, Xu Z. 2011. Antioxidant activity of a novel Streptomyces strain Eri12 isolated from the rhizosphere of rhizome Curcumae longae. Curr. Res. Bacteriol. 4: 63-72. doi: 10.3923/crb.2011.63.72
Published
2022-09-28
How to Cite
Jumina, J., Kurniawan, Y. S., Sari, R., Purba, S. N. H. B., Radean, H., Priatmoko, P., Pranowo, D., Purwono, B., Julianus, J., Zulkarnain, A. K., & Sholikhah, E. N. (2022). Synthesis and High Antioxidant Activity of C-Alkyl Calix[4]resorcinarene and C-Alkyl Calix[4]pyrogallolarene Derivatives . Indonesian Journal of Pharmacy, 33(3), 422-433. https://doi.org/10.22146/ijp.2199
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Research Article
