Studi in Silico Potensi Aktivitas Farmakologi Senyawa Golongan Dihidrotetrazolopirimidin

Abstract

Senyawa golongan dihidrotetrazolopirimidin dapat disintesis menggunakan Reaksi Biginelli. Senyawa etil 5-metil-7-(4-morfolinofenil)-4,7-dihidrotetrazolo[1,5a] pirimidin-6-karboksilat (MDP) merupakan senyawa organik baru terdiri atas cincin dihidrotetrazolopirimidin dengan gugus samping morfolinofenil. Penelitian sebelumnya menyebutkan bahwa senyawa pirimidin dan turunannya memiliki berbagai macam aktivitas farmakologi. Pada penelitian ini, senyawa MDP dianalisis menggunakan studi in silico untuk mengetahui potensi yang dimiliki sebagai agen terapi untuk mengatasi masalah kesehatan. Hasil analisis menunjukkan bahwa senyawa MDP berpotensi sebagai antimalaria, antikanker, dan antihiperurisemia dilihat dari binding energy yang bernilai negatif atau rendah. Interaksi senyawa MDP dengan reseptor yang bernilai paling negatif pada saat berinteraksi dengan protein XOD dibandingkan dengan nilai binding energy MDP dengan Kinesin Eg5 dan PfDHODH. Sehingga dapat disimpulkan bahwa senyawa MDP paling potensial jika digunakan sebagai antihiperurisemia dengan nilai binding energy sebesar -8,33 kkal/mol dengan konstanta inhibisi 0,79 µM.
 Kata kunci: antihiperurisemia, antikanker, antimalaria, dihidrotetrazolopirimidin, in silico
 Dihydrotetrazolopyrimidine derivatives can be synthezed using the Biginelli Reaction. Ethyl 5-methyl-7-(4-morpholinophenyl)-4,7-dihydrotetrazolo[1,5a]pyrimidine-6-carboxylate (MDP) is a new organic compound consisting of a dihydrotetrazolopyrimidine ring with morpholinophenyl moiety. Previous studies showed that pyrimidine compounds and their derivatives exhibited various pharmacological activities. In this study, MDP compound was analyzed using in silico studies to determine its potential to be used as therapeutic agent to overcome health problems. The results of the analysis showed that the MDP compound has potential activity as an antimalarial, anticancer, and antihyperuricemia, based on negative or low binding energy. The interaction of MDP compound with XOD protein showed the lowest binding energy compared to Kinesin Eg5 and PfDHODH. Based on the docking experiments performed, it can be concluded that MDP compound showed the most potential to be used as an antihyperuricemia with binding energy of -8.33 kcal/mol and inhibition concentration of 0,79 µM.
 Keywords: anticancer, antihyperuricemia, antimalarial, dihydrotetrazolopyrimidine, in silico

Molecular Docking and Dynamic Simulation of Erythrina fusca Lour Chemical Compounds Targeting VEGFR-2 Receptor for Anti-Liver Cancer Activity

“…The binding energy value and Ki are parameters of the conformational stability of the investigated compounds in terms of affinity towards VEGFR-2 receptor 15 . The binding energy value was obtained through the interaction of the ligand with a receptor, which showed the suitability between the shape and size of the ligand and the binding site on receptor 16 . Moreover, molecular docking results of the native ligand Sorafenib showed a binding energy of -11.51 kcal/mol and a Ki value of 3.67 nM.…”