SINTESIS TURUNAN HIDROKSIBENZOFENON DAN UJI AKTIVITASNYA SEBAGAI TABIR SURYA SERAPAN LEBAR SERTA ANTIOKSIDAN

ANGGIT FITRIA, Prof. Drs. Jumina, Ph.D. ; Prof. Dr. Harno Dwi Pranowo, M.Si.

2019 | Tesis | MAGISTER KIMIA

Sintesis 2,4,4'-trihidroksi-3'-metoksibenzofenon (6); 2,3,4,4'-tetrahidroksi-3'-metoksibenzofenon (7); 2,4,4'-trihidroksi-3-metil-3'-metoksibenzofenon (8a); 3,4',5-trihidroksi-4-metil-3'-metoksibenzofenon (8b) dan 3-heksil-2,4',6-tri-hidroksi-3'-metoksibenzofenon (9) telah dilakukan. Uji sitotoksisitas, aktivitas tabir surya, fotostabilitas, dan antioksidan senyawa 6-9 telah berhasil ditentukan. Sintesis turunan hidroksibenzofenon, yaitu 6-9 masing-masing dilakukan melalui reaksi asilasi antara asam vanilat (1) dengan turunan fenol berupa resorsinol (2), pirogalol (3), 2-metilresorsinol (4), atau 4-n-heksilresorsinol (5) dengan bantuan katalis CH3SO3H dan agen dehidrasi P4O10 (reagen Eaton). Masing-masing produk sintesis dimurnikan dengan kromatografi kolom menggunakan gradien eluen n-heksana : etil asetat (dari non polar ke polar) dilanjutkan analisis dengan scanner KLT. Produk hasil pemurnian dianalisis menggunakan spektrometer FTIR, direct inlet MS (DI–MS), 1H– dan 13C–NMR. Uji sitotoksisitas 6-9 dengan 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromida (MTT) dilakukan pada sel Vero. Senyawa 6-9 diformulasikan menjadi krim tabir surya (N6-9) dan diukur nilai Sun Protection Factor (SPF), panjang gelombang kritis (lamdakritis), peringkat perlindungan UVA, serta fotostabilitas. Senyawa 6-9 diuji aktivitas antioksidan dengan 2,2-difenil-1-pikrilhidrazil (DPPH). Eksperimen sintesis menghasilkan senyawa yang diinginkan dengan persen hasil untuk 6, 7, 8, dan 9 adalah masing-masing 61, 28, 10, dan 11%. Uji sitotoksisitas 6-9 menghasilkan nilai IC50 masing-masing 605, 699, 457, dan 279 mikrogram m/L. Krim yang telah dibuat dari 6-9 (N6-9) memiliki nilai SPF masing-masing 47, 70, 36, dan 17 dan tergolong tabir surya serapan lebar pada masing-masing lamdakritis 386, 386, 387, dan 387 nm dengan perlindungan UVA paling baik (peringkat perlindungan UVA = 4). Krim tabir surya (N6-9) menghasilkan sifat fotostabil sampai menit ke-90 yang diindikasikan dengan nilai SPF > 10. Senyawa 6-9 menunjukkan aktivitas antioksidan dengan nilai EC50 masing-masing sebesar 260; 3,36; 349; dan 386 mg/L daripada kontrol positif antioksidan, butil hidroksi toluen (BHT), yang memiliki EC50 sebesar 14,0 mg/L.

Synthesis of 2,4,4'-trihydroxy-3'-methoxybenzophenone (6); 2,3,4',4-tetrahydroxy-3'-methoxybenzophenone (7); 2,4,4'-trihydroxy-3'-methoxy-3-methylbenzophenone (8a); 3,4',5- trihydroxy-3'-methoxy-4-methylbenzophenone (8b) and 3-hexyl-2,4',6- trihydroxy-3'-methoxybenzophenone (9) have been carried out. Cytotoxicity, sunscreen activity, photostability, and antioxidant assays of 6-9 have been determined. Synthesis of hydroxybenzophenones, i.e. 6-9 have been conducted through acylation reaction between vanillic acid (1) and phenol derivatives, such as resorcinol (2), pyrogallol (3), 2-methylresorcinol (4), or 4-n-hexylresorcinol (5) with CH3SO3H catalyst and P4O10 as dehydration agent (Eaton's reagent), respectively. Each of synthesized products was purified using column chromatography with eluent gradient n-hexane : ethyl acetate (from non polar to polar) and the products were then analyzed using TLC scanner. The purified products were analyzed using FTIR, direct inlet MS (DI–MS), 1H– and 13C–NMR spectrometer. Cytotoxicity assay of 6-9 using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) were done in Vero cell line. Compounds 6-9 were formulated as sunscreen creams (N6-9) and were measured their Sun Protection Factor (SPF) values, critical wavelength (lamdacritical), UVA protection rating, and photostability. Compounds 6-9 were tested antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH). The synthesis experiments afforded the expected products in the percent yield for 6-9 were 61, 28, 10, dan 11%, respectively. The results of the 6-9 cytotoxicity assay produced IC50 values of 605, 699, 457, and 279 mikrogram/mL, respectively. Sunscreen creams made from 6-9 (N6-9) have SPF values of 47, 70, 36, and 17 respectively and are classified as broad spectrum sunscreens at critical 386, 386, 387, and 387 nm respectively with UVA protection is best (UVA protection rating = 4). The creams (N6-9) produced photostable properties up to 90 minutes that is indicated with SPF values > 10. Compounds 6-9 show antioxidant activity with an EC50 value of 260; 3.36; 349; and 386 mg/L respectively compared to positive antioxidant control, butylated hydroxytoluene (BHT), having an EC50 of 14.0 mg/L.

Kata Kunci : antioksidan, fotostabilitas, hidroksibenzofenon, reagen Eaton, sitotoksisitas, antioxidant, cytotoxicity, Eaton’s reagent, hydroxybenzophenone, photostability