STUDI HKSA SENYAWA ANALOG QUINOLON-4(1H)-IMINE SEBAGAI ANTIMALARIA MENGGUNAKAN PERHITUNGAN HARTHREE-FOCK

Jafar La Kilo, Akram La Kilo

Abstract


Penelitian ini bertujuan untuk melakukan studi hubungan kuantitatif struktur-aktivitas (HKSA) terhadap senyawa analog Quinolon-4(1H)-imine sebagai agen antimalaria. Pendekatan HKSA digunakan untuk menghubungkan aktivitas biologi molekul dengan deskriptor yang dihasilkan dari perhitungan menggunakan metode kimia kuantum Harthree-Fock Sebanyak 22 senyawa turunan Quinolon-4(1H)-imine digunakan sebagai bahan kajian, dengan perhitungan deskriptor elektronik dan molekul yang berpengaruh terhadap aktivitas antimalaria. Model HKSA dianalisis menggunakan metode regresi linear berganda (MLR) dan delapan model persamaan HKSA terbaik dihasilkan. Model-model tersebut kemudian divalidasi dan model terbaik dipilih berdasarkan parameter statistik yang signifikan. Rancangan senyawa usulan juga dilakukan berdasarkan model terbaik, dengan mengganti substituen pada senyawa turunan Quinolon-4(1H)-imine. Hasil penelitian ini dapat memberikan kontribusi dalam pengembangan obat antimalaria baru dengan pendekatan teoritik dan pemodelan, sehingga dapat mengurangi biaya dan waktu yang diperlukan dalam penemuan dan pengembangan obat antibiotik baru.

Keywords


Senyawa analog Quinolon-4(1H)-imine; Pendekatan HKSA; Density Functional Theory (DFT); Pengembangan obat antimalaria

Full Text:

PDF

References


Andayi, W. A., Egan, T.J., Gut, J., Rosenthal, P.J.,Chibale, K., 2013, Synthesis, Antiplasmodial Activity, and β-Hematin Inhibition of Hydroxypyridone- Chloroquine Hybrids. ACS Med. Chem. Lett., 4,642-646.

Anonima, 2013, World Malaria Report 2013, WHO., Jeneva.

Anonimb, 1997, IUPAC Compendium of Chemical Terminology, 2nd ed.

Blackwell Scientific Publications, Oxford.

Anonimc, 2009, HyperChemTM 8.0.10 for Windows. Hypercube Inc., Tulsa. Anonimd, 2007, SPSS® Release 16.0.0. SPSS Inc., USA.

Arief, I., 2013, Kajian Aktivitas Anti-HIV dan Sitotoksisitas Senyawa Turunan Diarilanilina dengan Metode Hubungan Kuantitatif Struktur-Aktivitas (HKSA), Tesis, Jurusan Kimia FMIPA UGM, Yogyakarta.

Batagin-Neto, A. & Lavarda, F.C., 2013, The correlation Between Electronic Structure and Antimalarial Activity of Alkoxylated and Hydroxylated Chalcones. Med. Chem. Res.

Beheshti, A., Pourbasheer, E. & Nekoei, M., 2012, QSAR Modeling of Antimalarial Activity of Urea Derivatives Using Genetic Algorithm - Multiple Linear Regressions. J. Saudi Chem. Soc.

Bhattacharya, A., Mishra, L.C., Sharma, M., Awasthi, S.K, Bhasin, V.K., 2009, Antimalarial Pharmacodynamics of Chalcone Derivatives in Combination with Artemisinin Against Plasmodium falciparum in vitro. Eur. J. Med. Chem., 44(9), 3388-3393.

Cardoso, F.J.B., Figueiredo, A.F., Lobato, M.S., Miranda, R.M., Almeida, R.C., Pinheiro, J.C., 2008, A study on Antimalarial Artemisinin Derivatives Using MEP Maps and Multivariate QSAR. J. Mol. Model., 14, 39-48.

Casabianca, L.B. & Dios, A.C., 2006. Relationship between NMR Shielding and Heme Binding Strength for a Series of 7-Substituted Quinolines. J. Phys. Chem. A, 110, 7787-7792.

Cramer, C.J., 2004. Essentials of Computational Chemistry, Second Edition, John Wiley & Sons Ltd., Chichester.

Cui, X., Vlahakis, J. Z., Crandall, E., & Szarek, W. A., 2008, Anti- Plasmodium Activity of Tetrazolium Salts. Bioorg. Med. Chem., 16, 1927-1947.

Damme, S.V., 2009, Quantum Chemistry in QSAR, Quantum Chemical Descriptors, Use, Benefits and Drawbacks, Thesis, Departments of Inorganic and Physical Chemistry Faculty of Sciences Universiteit Gent, Netherland.

Etrawati, F., 2012, Intervensi Perilaku dan Lingkungan Dalam Pencegahan Kejadian Penyakit Malaria di Indonesia Tahun 2012. Buletin SPIRAKEL edisi 2012, 25-32.

Frimayanti, N., Yam, M.L., Lee, H.B., & Othman, R., 2011, Validation of Quantitative Structure-Activity Relationship (QSAR) Model for Photosensitizer Activity Prediction. Int. J. Mol. Sci., 12, 8626-8644.

Frisch, M.J, Trucks, G.W, Schlegel, H.B, Scuseria, G.E, Robb, M.A, Cheeseman, J.R, Scalmani, G, Barone, V, Mennucci, B, Petersson, G.A, Nakatsuji, H, Caricato, M, Li, X, Hratchian, M.A, Izmaylov, F, Bloino, F, Zheng, G, Sonnenberg, J.L, Hada, J.L, Ehara, M, Toyota, K, Fukuda, R, Hasegawa, R Ishida, M, Nakajima, T, Honda,Y, Kitao, O, Nakai, H, Vreven, T, Montgomery, J.A, Peralta, Jr., J.E, Ogliaro, F, Bearpark, M, Heyd, J.J, Brothers, E.K, Kudin, N, Staroverov, N, Kobayashi, Normand, J, Raghavachari, Rendell, K A, Burant, J.C, Iyengar, S.S, Tomasi, J, Cossi, M Rega, N, Millam, J.M, Klene, M, Knox, J.E, Cross, J.B, Bakken, V, Adamo, C, Jaramillo, J, Gomperts, C, Stratmann, R.E, Yazyev, O, Austin, A.J,. Cammi, RC, Pomelli, Ochterski, J.W, Martin, R.L, Morokuma, K, Zakrzewski, VG, Voth, .A. Salvador, GA, Dannenberg, J.J, Dapprich, S, Daniels, A.D, Farkas, O, Foresman, J.B, Ortiz, J.V, Cioslowski, J and Fox, DJ, 2009, Gaussian Inc., Wallingford CT.

Gironés, X., Gallegos, A & Carbó-Dorca, R., 2000, Modeling Antimalarial Activity: Application of Kinetic Energy Density Quantum Similarity Measures as Descriptors in QSAR. J. Chem. Inf. Comput. Sci., 40(6), 1400- 1407.

Golbraikh, A., Shen, M., Xiao, Z., Xiao, Y., & Lee, K., 2003, Rational Selection of Training and Test Sets for the Development of Validated QSAR Models. J. Comp.-Aid. Mol. Des., 17, 241-253.

Goncalves, N. S., Cristiano, R., Geraldo, M., & Miranda, S., 2005. Vibrational analysis and NMR properties based on ab initio and DFT calculations of two naturally occurring xanthones : J. of Mol. Struc., 733, 53-61.

Hay, A.E., Hélesbeux, J.J., Duval, O., Labaïed, M., Grellier, P., & Richomme, P., 2004, Antimalarial Xanthones from Calophyllum caledonicum and Garcinia vieillardii. Lif. Sci., 75(25), 3077-85

Hwang, J. Y., Kawasuji, T., Lowes, D. J., Clark, J. A., Connelly, M. C., Zhu, F., Guy, R.K., 2011, Synthesis and Evaluation of 7-Substituted 4- Aminoquinoline Analogues for Antimalarial Activity. J. Med. Chem., 54, 7084-7093.

Ibezim, E., Duchowicz, P. R., Ortiz, E. V., & Castro, E. A., 2012, QSAR on Aryl- piperazine Derivatives with Activity on Malaria. Chem. Intel. Lab. Syst. , 110(1), 81-88.

Jaiswal, M. & Khadikar, P., 2004. QSAR study on 13 C NMR chemical shifts on carbinol carbon atoms. Bioorg. Med. Chem., 12,1793-1798.

Jensen, F., 2007, Introduction to Computational Chemistry, Second Edition, John Wiley & Sons Ltd., Chichester.

Karelson, M., Lobanov, V.S. & Katritzky, A.R., 1996, Quantum-Chemical Descriptors in QSAR/QSPR Studies. Chem. Rev., 96(3), 1027-1044.

Katritzky, A. R., Kuanar, M., Dobchev, D. A, Vanhoecke, B. W. A, Karelson, M., Parmar, V. S.,Bracke, M. E., 2006, QSAR Modeling of Anti-invasive Activity of Organic Compounds Using Structural Descriptors. Bioorg. Med. Chem., 14(20), 6933-6939.

Katritzky, A. R., Kuanar, M., Slavov, S., Hall, C. D., Karelson, M., Kahn, I., & Dobchev, D. A., 2010, Quantitative Correlation of Physical and Chemical Properties with Chemical Structure: Utility for Prediction. Chem. Rev., 110(10), 5714-5789.

Kaur, K., Jain, M., Reddy, R. P., & Jain, R., 2010, Quinolines and Structurally Related Heterocycles as Antimalarials. Eur. J. Med. Chem., 45(8), 3245- 3264.

Khadikar, P. V, Sharma, V., Supuran, C. T., Chimica, D., Bioinorganica, C., & Sest, S., 2005. Novel use of chemical shift in NMR as molecular descriptor: a first report on modeling carbonic anhydrase inhibitory activity and related parameters. Bioorg. Med. Chem., 15, 931-936.

Lane, A. L., Stout, E. P., Lin, A.-S., Prudhomme, J., Le Roch, K., Fairchild, C. R., Kubanek, J., 2009, Antimalarial Bromophycolides J-Q From the Fijian Red Alga Callophycus serratus. J. Org. Chem., 74(7), 2736-2742.

Le, T., Epa, V. C., Burden, F. R., & Winkler, D. A., 2012, Quantitative Structure- Property Relationship Modeling of Diverse Materials Properties. Chem. Rev., 112(5), 2889-919.

Li, J., Li, S., Bai, C., Liu, H., & Gramatica, P., 2013, Structural Requirements of 3-Carboxyl-4(1H )-Quinolones as Potential Antimalarials from 2D and 3D QSAR Analysis. J. Mol. Graph. Model., 44, 266-277.

Likhitwitayawuid, K., Phadungcharoen, T. & Krungkrai, J., 1998, Antimalarial Xanthones from Garcinia cowa. Plant. Med., 64, 70-72.

Manohar, S., Khan, S. I., Kandi, S. K., Raj, K., Sun, G., Yang, X., "¦ Rawat, D. S., 2013, Synthesis, Antimalarial Activity and Cytotoxic Potential of New Monocarbonyl Analogues of Curcumin. Bioorg. Med. Chem. Lett., 23(1), 112-116.

Michielan, L. & Moro, S., 2010, Pharmaceutical Perspectives of Nonlinear QSAR Strategies. J. Chem. Inf. Model., 50(6), 961-978.

Mishra, M., Mishra, V. K., Senger, P., Pathak, A. K., & Kashaw, S. K., 2013, Exploring QSAR Studies on 4-substituted Quinazoline Derivatives as Antimalarial Compounds for the Development of Predictive Models. Med. Chem. Res.

Molyneaux, C., Krugliak, M., Ginsburg, H., & Chibale, K., 2005, Arylpiperazines displaying preferential potency against chloroquine-resistant strains of the malaria parasite Plasmodium falciparum. Biochem. Pharm., 71, 61-68

Motta, L.F. & Almeida, W.P., 2011. Quantitative Structure-Activity Relationships (QSAR) of A Series of Ketone Derivatives as Anti-Candida Albicans. Int. J. Dru. Disc., 3(2), 100-117.

Nantasenamat, C., Isarankura-na-ayudhya, C. & Naenna, T., 2009, Review Article : A Practical Overview of Quantitative Structure-Activity Relationship. EXCLI Journal, 8, 74-88.

Nepveu, F., Kim, S., Boyer, J., Chatriant, O., Ibrahim, H., Reybier, K., Nallet, J.P., 2010, Synthesis and Antiplasmodial Activity of New Indolone N-oxide Derivatives. J. Med. Chem., 53(2), 699-714.

Ohno, K., 2004, Buka Teks Kimia Kuantum Online (diterjemahkan oleh Prijamboedi, B), http://www.inorg-phys.chem.itb.ac.id/index.php/en/teaching

/1-buku-kuliah/6-kimia-kuantum-koici-ohno-bambang-prijamboedi-terj., diakses 22 Juni 2014.

Podunavac-kuzmanovic, S.O., Cvetkovi, D.D. & Barna, D.J., 2009, QSAR Analysis of 2-Amino or 2-Methyl-1-Substituted Benzimidazoles Against Pseudomonas aeruginosa. Int. J. Mol. Sci., 10, 1670-1682.

Ressurreição, A. S., Gonçalves, D., Sitoe, A. R., Albuquerque, I. S., Gut, J., Góis, A., Moreira, R., 2013, Structural Optimization of Quinolon-4(1H)-imines as Dual-stage Antimalarials: Toward Increased Potency and Metabolic stability. J. Med. Chem., 56(19), 7679-7690.

Roy, K. & Roy, P.P., 2009, Comparative Chemometric Modeling of Cytochrome 3A4 Inhibitory Activity of Structurally Diverse Compounds Using Stepwise MLR , FA-MLR , PLS , GFA , G/PLS and ANN Techniques. Eur. J. Med. Chem., 44(7), 2913-2922.

Saghaie, L., Sakhi, H., Sabzyan, H., Shahlaei, M., & Shamshirian, D., 2013, Stepwise MLR and PCR QSAR Study of the Pharmaceutical Activities of Antimalarial 3-hydroxypyridinone Agents Using B3LYP / 6-311++G** Descriptors. Med. Chem. Res., 22, 1679-1688.




DOI: https://doi.org/10.34312/jambchem.v4i1.20008

Refbacks

  • There are currently no refbacks.


Copyright (c) 2022 Jambura Journal of Chemistry



EDITORIAL OFFICE

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.