QUANTITAVE STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS (QSAR) OF ANTIMALARIAL 1,10-PHENANTHROLINE DERIVATIVES COMPOUNDS

https://doi.org/10.22146/ijc.21716

Ruslin Hadanu(1*), Sabirin Mastjeh(2), Mustofa Mustofa(3), Eti Nurwening Sholikhah(4), Mahardika Agus Wijayanti(5), Iqmal Tahir(6)

(1) Department of Chemistry, FKIP, Pattimura University, Poka, Ambon- Indonesia,
(2) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Gadjah Mada University, Sekip Utara, Yogyakarta-Indonesia 55281
(3) Department of Pharmacology and Toxicology, Faculty of Medicine, Gadjah Mada University, Sekip Utara, Yogyakarta-Indonesia 55281
(4) Department of Pharmacology and Toxicology, Faculty of Medicine, Gadjah Mada University, Sekip Utara, Yogyakarta-Indonesia 55281
(5) Department of Parasitology, Faculty of Medicine, Gadjah Mada University, Sekip Utara, Yogyakarta-Indonesia 55281
(6) Austrian-Indonesian Centre for Computational Chemistry, Faculty of Mathematics and Natural Sciences, Gadjah Mada University, Sekip Utara, Yogyakarta, Indonesia 55281
(*) Corresponding Author

Abstract


Quantitative Electronic Structure-Activity Relationship (QSAR) analysis of a series of 1,10-phenanthroline derivatives as antiplasmodial compounds have been conducted using atomic net charges (q), dipole moment (μ) ELUMO, EHOMO, polarizability (α) and log P as the descriptors. The descriptors were obtained from computational chemistry method using semi-empirical PM3. Antiplasmodial activities were taken as the activity of the drugs  against  chloroquine-resistant Plasmodium falciparum FCR3 strain and are presented as the value of ln (1/IC50) where IC50 is an effective concentration inhibiting 50% of the parasite growth. The best model of QSAR model was determine by multiple linear regression method and giving equation of QSAR:

ln 1/IC50  =  3.732 + (5.098) qC5 + (7.051) qC7 + (36.696) qC9 + (41.467) qC11 -(135.497) qC12 + (0.332) μ -

                   (0.170) α + (0.757) log P.

The equation was significant on the 95% level with statistical parameters: n=16; r=0.987; r2= 0.975; SE=0.317;  Fcalc/Ftable = 15.337 and gave the PRESS=0.707. Its means that there were only a relatively few deviations between the experimental and theoretical data of antimalarial activity.


Keywords


QSAR; antimalarial; semi-empirical method; 1,10-phenanthroline

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DOI: https://doi.org/10.22146/ijc.21716

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