SINTESIS SENYAWA ANALOG KURKUMIN MONOKARBONIL ASIMETRIS SERTA PENAMBATAN MOLEKUL DENGAN TARGET PROTEIN Pf-DHFR-TS SEBAGAI ANTIMALARIA

NUR HIDAYAH, Prof. Drs. Bambang Purwono, M.Sc. Ph.D.

2022 | Skripsi | S1 KIMIA

Telah dilakukan sintesis senyawa analog kurkumin monokarbonil asimetris serta penambatan molekul sebagai antimalaria. Sintesis analog kurkumin monokarbonil asimetris dilakukan melalui dua tahap reaksi yaitu sintesis benzalaseton dilanjutkan kondensasi benzalaseton dengan benzaldehid tersubstitusi. Benzaldehid tersubstitusi direaksikan dengan aseton dalam pelarut etanol dengan katalis basa NaOH 8% (b/v) dengan pengadukan selama 24 jam menghasilkan senyawa benzalaseton. Senyawa benzalaseton A [(E)-4-(4-hidroksil-3-metoksifenil) but-3-en-2-on] dihasilkan dari vanilin dan benzalaseton B [(E)-4-(2-hdroksifenil)but-3-en-2-on] dihasilkan dari salisilaldehid. Sintesis senyawa analog kurkumin monokarbonil asimetris (AKMA) diperoleh melalui reaksi antara benzalaseton dengan benzaldehid lain dengan perbandingan (1:1) dengan pelarut etanol dan menggunakan katalis basa NaOH 8% (b/v) dengan pengadukan selama 24 jam. AKMA 1 [1-(3-metoksi-4-hidroksifenil)-5-(4-metoksifenill)-penta-1,4-dien-3-on] dihasilkan dari reaksi benzalaseton A dengan senyawa p-anisaldehid dan AKMA 2 [1-(2-hidroksifenil)-5-(3-4-dimetoksifenill)penta-1,4-dien-3-on] dari benzalaseton B dengan senyawa veratraldehid. Elusidasi struktur terhadap produk hasil sintesis dilakukan dengan spektrometer FTIR, GC/LC-MS dan 1H-NMR. Senyawa AKMA 1 dan AKMA 2 diuji aktivitasnya sebagai senyawa antimalaria secara in silico dengan penambatan molekul terhadap protein Pf-DHFT-TS dan dilakukan analisis ADMET untuk mengetahui aktivitas biologisnya secara oral. Hasil penelitian diperoleh masing-masing benzalaseton A dan B dengan rendemen 58,6% dan 54,57% sedang AKMA 1 dengan rendemen 83,87% dan AKMA 2 dengan rendemen 61,29%. Hasil uji aktivitas melalui penambatan molekul menunjukkan bahwa AKMA 1 dan AKMA 2 memiliki aktivitas antimalaria yang lebih baik dengan nilai energi afinitas -7,03 kkal/mol dan -7,64 kkal/mol. Hasil prediksi ADMET menunjukkan bahwa senyawa AKMA 1 dan AKMA 2 bersifat non toxic dan sesuai dengan standar Lipinski's rule sehingga berpotensi dapat dikonsumsi secara oral.

Synthesis of asymmetric monocarbonyl curcumin analogue compounds and molecular docking as antimalarial has been carried out. Synthesis of asymmetric monocarbonyl curcumin analogues was carried out through two-step reaction, namely synthesis of benzalacetone followed by condensation of benzalacetone with substituted benzaldehyde. Substituted benzaldehyde was reacted with acetone in ethanol solvent with a base catalyst of 8% (w/v) NaOH with stirring for 24 hours to produce benzalacetone compound. Benzalacetone A [(E)-4-(4-hydroxyl-3-methoxyphenyl) but-3-en-2-one] is produced from vanilin and benzalacetone B [(E)-4-(2-hydroxyphenyl)but-3-en- 2-on] is produced salicylaldehyde. Synthesis of the asymmetric monocarbonyl curcumin analogue (AKMA) was obtained by reaction between benzalacetone and other benzaldehyde in ratio (1:1) with ethanol as a solvent and using a base catalyst of 8% (w/v) NaOH with stirring for 24 hours. AKMA 1 [1-(3-methoxy-4-hydroxyphenyl)-5-(4-methoxyphenyl)-penta-1,4- diene-3-one] was made from the reaction of benzalacetone A with compound p-anisaldehyde and AKMA 2 [1-(2-hydroxyphenyl)-5-(3-4-dimethoxyphenyl)penta-1,4-diene-3-one] was made from benzalacetone B with veratraldehyde. Structural elucidations of the synthesized product were carried out using FTIR, GC/LC-MS and 1H-NMR spectrometers. AKMA 1 and AKMA 2 were tested for their activity as antimalarial compounds in silico with molecular docking against Pf-DHFT-TS protein and ADMET analysis was performed to determine their biological activity orally. The results showed that benzalacetone A and B were produced in yield of 58.6% and 54.57%, while AKMA 1 and AKMA 2 was yielde in 83.87% and 61.29% respectively. The results of the activity test through molecular docking showed that AKMA 1 and AKMA 2 had better antimalarial activity with affinity energy values of -7.03 kcal/mol and -7.64 kcal/mol. ADMET prediction results show that AKMA 1 and AKMA 2 are non-toxic and conform Lipinski's rule standards so that they can potentially be consumed orally.

Kata Kunci : analog kurkumin monokarbonil asimetris, antimalaria, benzalaseton, penambatan molekul