DESAIN DAN SINTESIS SENYAWA ANALOG MONOKARBONIL KURKUMIN ASIMETRIS SEBAGAI SENYAWA ANTIMALARIA

NUR FIKRI AMALIA, Prof. Drs. Bambang Purwono, M.Sc, Ph.D.

2022 | Skripsi | S1 KIMIA

Desain dan sintesis senyawa analog monokarbonil kurkumin asimetris (AMKA) sebagai senyawa antimalaria telah dilakukan. Desain senyawa antimalaria dilakukan melalui penambatan molekul terhadap protein PfDHFR-TS dan analisis ADMET terhadap senyawa analog monokarbonil kurkumin asimetris (AMKA). Sintesis senyawa AMKA dilakukan melalui reaksi kondensasi Claisen-Schimdt terhadap senyawa benzalaseton dengan turunan benzaldehid. Benzalaseton disintesis dari reaksi kondensasi Claisen-Schmidt vanilin atau o-vanilin dengan aseton menggunakan katalis NaOH 8 %. Elusidasi struktur produk dilakukan menggunakan spektrometer FTIR, GC-MS, ¹H NMR dan ¹³C-NMR. Penambatan molekul menghasilkan tiga senyawa AMKA yang memiliki interaksi dengan tingkat energi terendah yakni AMKA A -7,83 kkal/mol, AMKA D -7,31 kkal/mol dan AMKA E -7,90 kkal/mol. AMKA A, D dan E memiliki profil ADMET yang lebih baik sebagai senyawa obat oral dibandingkan dengan kurkumin. Sintesis AMKA A, D dan E berhasil dilakukan melalui senyawa intermediat benzalaseton A dan benzalaseton B dengan rendemen berturut-turut 91,3; 67,8 dan 74,1 %.

Design and synthesis of an asymmetric monocarbonyl analogue of curcumin (AMKA) as an antimalarial compound have been carried out. The design of the antimalarial compound was carried out by molecular docking using PfDHFR-TS as protein target and ADMET analysis of the AMKA. The synthesis of AMKA was carried out through a Claisen-Schimdt condensation reaction of benzalacetone with benzaldehyde derivatives. Benzalacetone is synthesized from the Claisen-Schmidt condensation reaction of vanillin or o-vanillin with acetone using 8 % NaOH as a catalyst. The structure elucidation of the product was carried out using FTIR, GC-MS, 1H NMR and 13C-NMR spectrometers. Molecular docking resulted three proposed AMKA compounds having the lowest affinity interactions, AMKA A -7.83 kcal/mol, AMKA D -7.31 kcal/mol and AMKA E -7.90 kcal/mol, respectively. AMKA A, D and E had a better ADMET analysis as an oral drug compound compared to curcumin. The synthesis of AMKA A, D and E was successfully carried out through the benzalacetone A and benzalacetone B with yields of 91.3, 67.8 and 74.1 % respectively.

Kata Kunci : ADMET, AMKA, Antimalaria, penambatan molekul