SINTESIS SENYAWA N-FENIL DAN N-ASETILPIRAZOLINA MELALUI INTERMEDIET DIBENZALASETON DAN UJI AKTIVITAS ANTIMALARIANYA

LINDA EKAWATI, Drs. Bambang Purwono, M.Sc., Ph.D. ; Dr. M. Idham. D. Mardjan, S.Si., M.Sc.

2019 | Tesis | MAGISTER KIMIA

Sintesis senyawa dibenzalaseton (1,5-difenilpenta-1,4-dien-3-on (5); 1,5-bis(3,4-dimetoksifenil)penta-1,4-dien-3-on/(6);/1,5-bis(4-metoksifenil)-penta-1,4- dien-3-on (7)); dan senyawa N-fenilpirazolina (1,5-difenil-3-stiril-4,5-dihidro-1H-pirazol (9); 5-(3,4-dimetoksifenil)-3-(3,4-dimetoksistiril)1-fenil-4,5-dihidro-1H-pirazol (10); 5-(4-metoksifenil)-3-(4-metoksistiril-1-fenil-4,5-dihidro-1H-pirazol (11)); serta senyawa N-asetilpirazolina (1-(5-fenil-3-stiril-4,5-dihidro-1H-pirazol-1-il)etanon/(14);/1-(5-(3,4-dimetoksifenil)-3-(3,4-dimetoksistiril)-4,5-dihidro-1H-pirazol-1-il)etanon (15); 1-(5-(4-metoksifenil)-3-(4-metoksistiril)-4,5-dihidro-1H-pirazol-1-il)etanon (16)) telah dilakukan. Aktivitas antimalaria senyawa 5-7, 9-11 dan 14-16 telah berhasil ditentukan melalui uji aktivitas penghambatan polinmeisasi hem. Sintesis senyawa dibenzalaseton 5-7 dilakukan melalui kondensasi Claisen-Schmidt antara aseton (1) dengan turunan benzaldehida berupa benzaldehida (2), veratraldehida (3) dan p-anisaldehida (4) dengan katalis natrium hidroksida (NaOH). Senyawa turunan N-fenilpirazolina 9-11 diperoleh melalui reaksi siklokondensasi antara senyawa 5-7 dan fenilhidrazin (8) dengan asam asetat (CH3COOH) sebagai katalis. Senyawa N-asetilpirazolina diperoleh dari reaksi siklokondensasi antara senyawa 5-7 dan hidrazinhidrat (12) dengan asam asetat (13) sebagai katalis dan reagen. Produk hasil sintesis dianalisis menggunakan spektrometer FTIR, direct inlet-MS (DI-MS), GC-MS, 1H- dan 13C-NMR. Sintesis senyawa 5, 6, 7, 9, 10, 11, 14, 15 dan 16 dihasilkan dengan persen hasil berturut-turut adalah 97,65; 90,96; 70,75; 82,17; 70,45; 88,31; 73,27; 56,10; dan 77,14 %. Uji aktivitas penghambatan polimerisasi hem senyawa tersebut menghasilkan nilai IC50 masing-masing 1,23; 0,49; 1,39; 1,26; 0,79; 1,08; 3,47; 1,39; dan 3,16 mM. Nilai IC50 senyawa hasil sintesis dibawah dari nilai IC50 kuinin sebagai kontrol positif sehingga senyawa hasil sintesis berpotensi dikembangkan sebagai kandidat antimalaria.

Synthesis of dibenzalacetones (1,5-diphenylpenta-1,4-dien-3-one (5); 1,5-bis(3,4-dimetoxyphenyl)penta-1,4-dien-3-one (6);//1,5-bis(4-metoxyphenyl)-penta -1,4-dien-3-one/(7));/and/N-phenylpyrazolines (1,5-diphenyl-3-styryl-4,5-dihydro-1H-pyrazole/(9); 5-(3,4-dimetoxyphenyl)-3-(3,4-dimetoxystyryl)-1-phenyl-4,5-dihydro-1H-pyrazole (10); 5-(4-metoxyphenyl)-3-(4-metoxystyryl)-1-phenyl-4,5-dihydro-1H-pyrazole-(11)); as well as N-acetylpyrazolines (1-(5-phenyl-3-styryl-4,5-dihydro-1H-pyrazole-1-yl)etanone/(14);/1-(5-(3,4-dimetoxyphenyl)-3-(3,4- dimetoxystyryl)-4,5-dihydro-1H-pyrazole-1-yl)etanone/(15); 1-(5-(4-methoxyphe- nyl)-3-(4-methoxystyryl)-4,5-dihydro-1H-pirazole-1-yl)etanone (16)) have been carried out. Antimalarial activity assay of compounds 5-7; 9-11 and 14-16 have been determined by Heme Polymerization Inhibitory Activity (HPIA) assay. Synthesis of dibenzalacetones 5-7 have been conducted via Claisen-Schmidt condensation between acetone (1) and benzaldehyde derivatives, such as benzaldehyde (2), veratraldehyde (3) and p-anisaldehide (4) with sodium hydroxide (NaOH) as catalyst. N-phenylpyrazolines 9-11 can be produced via cyclocondensation reaction between dibenzalacetones 5-7 and phenylhidrazine (8) with acetic acid (CH3COOH) as catalyst. N-acetylpyrazolines of 14-16 can be obtained via cyclocondensation reaction between dibenzalacetones 5-7 and hydrazinhydrate (12) with acetic acid (13) as catalyst and reagent. Products were analyzed using FTIR spectrometry, direct inlet-MS (DI-MS), GC-MS, 1H- and 13C-NMR. The synthesis experiments afforded the expected product were the yields for 5, 6, 7, 9, 10, 11, 14, 15 and 16 were 97.65; 90.96; 70.75; 82.17; 70.45; 88.31; 73.27; 56.10; and 77.14 % respectively. The result of Heme Polymerization Inhibition Activity assay gave IC50 value of 1.23; 0.49; 1.39; 1.26; 0.79; 1.08; 3.47; 1.39; and 3.16 mM respectively under IC50 value of quinine as positive control. Based on the IC50 value, compounds 5-7, 9-11 and 14-16 potential as antimalarial candidates. Keywords: antimalaria, dibenzalacetone, HPIA, N-acetylpirazoline, N-phenylpirazoline

Kata Kunci : antimalaria, dibenzalaseton, penghambatan polimerisasi hem, N-asetilpirazolina, N-fenilpirazolina, antimalaria, dibenzalacetone, HPIA, N-acetylpirazoline, N-phenylpirazoline