NOVEL DESIGN OF CALANONE DERIVATIVES AS ANTI-LEUKEMIA COMPOUNDS BASED ON QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS

Ponco Iswanto (Chemistry Department, Faculty of Science and Engineering, Universitas Jenderal Soedirman, Karangwangkal, Purwokerto 53122)
Mochammad Chasani (Chemistry Department, Faculty of Science and Engineering, Universitas Jenderal Soedirman, Karangwangkal, Purwokerto 53122)
Harjono Harjono (Chemistry Department, Faculty of Science and Engineering, Universitas Jenderal Soedirman, Karangwangkal, Purwokerto 53122)
Iqmal Tahir (Austrian-Indonesian Centre for Computational Chemistry (AIC), Chemistry Department, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281)
Muhammad Hanafi (Chemistry Research Centre, Indonesian Institute of Sciences (LIPI), PUSPIPTEK Serpong, Banten 15314)
Eva Vaulina YD (Chemistry Department, Faculty of Science and Engineering, Universitas Jenderal Soedirman, Karangwangkal, Purwokerto 53122)

Indonesian Journal of Chemistry
Vol 11, No 1 (2011)

Leukemia drug discovery based on calanone compound was conducted in previous research and produced 6 calanone derivatives. Most of them have lower activities against leukemia cell L1210 than pure calanone. A Quantitative Structure-Activity Relationship (QSAR) analysis is conducted in this work to find more active calanone derivatives. Six compounds were used as the material of the research because they already have anti-leukemia activity data expressed in Inhibitory Concentration of Fifty Percent Cell Lethal (IC50, in mg/mL). Calculation of predictors was performed by AM1 semiempirical method. QSAR equation is determined using Principle Component Regression (PCR) analysis, with Log IC50 as dependent variable. Independent variables (predictors) are atomic net charges, dipole moment (m), and coefficient partition of n-octanol/water (Log P). This work recommends 3 novel designs of calanone derivatives that may have higher activities (in mg/mL) than those already available, i.e. gemdiol calanone (57.78), 2,4-dinitrophenylhydrazone calanone (30.94) and 2,4,6-trinitrophenylhydrazone calanone (18.96).