ANALISIS HUBUNGAN KUANTITATIF STRUKTUR DAN AKTIVITAS ANTIMALARIA SENYAWA TURUNAN QUINOXALIN

M. Noor, K. Kasmui, S. B. W. Kusuma

Abstract


Quinoxalin merupakan senyawa heterosiklik yang memiliki cincin benzena dan pirazin. Turunan quinoxalin yaitu 3-fenilquinoxalin 1,4-di N-oksida merupakan senyawa antimalaria yang berpotensi dan perlu dikaji. Kajian hubungan kuantitatif struktur dan aktivitas (HKSA) antimalaria senyawa turunan quinoxalin menggunakan deskriptor hidrofobik dan elektronik. Optimasi model senyawa turunan quinoxalin menggunakan metode DFT dengan basis set 6311G menggunakan program Gaussian09W, dan nilai deskriptor diperoleh berdasarkan perhitungan kimia komputasi menggunakan program Gaussian09W dan MarvinBeans. Data deskriptor digunakan untuk menghitung nilai Log 1/IC50 dan dibandingkan dengan data eksperimen dari literatur. Hasil perhitungan dianalisis menggunakan metode regresi multilinear sehingga diperoleh persamaan HKSA:

Log 1/IC50 = 31,890+ (-57,754) qC8+ (6,537) qC7+ (-770,959) qC10+ (-10,387) qC15+ (0,008) MSA+ (-0,532) Log P+ (-10,941)HOMO+ (0,285) momen dipol

(n=12,R=0,976,R2=0,953,SE= 0,1305, PRESS = 0,174)

Berdasarkan persamaan HKSA tersebut, didapatkan prediksi turunan senyawa quinoxalin dengan subtituen pendonor etoksi dan etil yang memiliki aktivitas antimalaria yang lebih baik daripada pendonor metoksi dan metil.

Quinoxaline is a heterocyclic compound containing a ring complex made up of benzene and pyrazine. Its derivative 3-phenylquinoxaline 1,4-di N-oxide is a potential antimalaria and need to be developed. Quantitative Structure-Activity Relationship Analysis (QSAR) of quinoxaline as antimalarial drug has been conducted using electronic and hydrofobic descriptor. Optimization of an analog quinoxaline using DFT method with 6311G for basis set. The calculation for optimization obtained by using Gaussian09W program. Descriptor values obatained by using Gaussian09W program and Marvin Beans. Log 1/IC50 is determined from descriptor values and compared with the experimental data. The equation is:

Log 1/IC50 = 31,890+ (-57,754) qC8+ (6,537) qC7+ (-770,959) qC10+ (-10,387) qC15+ (0,008) MSA+ (-0,532) Log P+ (-10,941)HOMO+ (0,285) moment dipole

(n=12,R=0,976,R2=0,953,SE= 0,1305, PRESS = 0,174)

Based on QSAR equation, the potential of quinoxaline prediction compounds with ethoxy and ethyl group subtituent yield good antimalarial activity than methoxy and methyl subtituent.


Keywords


quinoxaline; antimalarial; QSAR

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References


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