Analysis of a Quantitative Relationship Between the Structure and Analgesic Activity of Meperidin Derivatives Using Semi-Empirical AM1 Method

Abstract

ABSTRAKPenelitian ini bertujuan untuk melakukan analisis hubungan kuantitatif antara struktur dan aktivitas analgesik senyawa turunan meperidin dan menentukan persamaan Hansch antara senyawa turunan meperidin dengan aktivitas analgesiknya. Penelitian dilakukan melalui perhitungan komputer (in silico) dengan menggunakan metode semiempiris AM1. Tahap pertama yaitu melakukan pemodelan molekul senyawa turunan meperidin, kemudian melakukan proses optimasi geometri. Langkah kedua yaitu melakukan pencarian nilai deskriptor yang berupa deskriptor elektronik, sterik, dan hidrofobik. Tahap terakhir dilakukan analisis statistik menggunakan regresi berganda model Backward. Hasil penelitian menunjukkan bahwa aktivitas analgesik dipengaruhi secara signifikan oleh variasi deskriptor, terutama deskriptor elektronik yang memiliki pengaruh lebih dominan daripada deskriptor sterik dan hidrofobik. Deskriptor yang paling berpengaruh adalah muatan pada atom N, karena atom N merupakan komponen penting dalam senyawa analgesik. Kata kunci: turunan Meperidin, aktivitas analgesik, deskriptor elektronik, persamaan Hansch ABSTRACTThis research aims were to analize a quantitative relationship between the structure and analgesic activity of meperidine derivatives and to determine the Hansch equation between meperidine derivatives and their analgesic activity. The study was done by computer calculation (in sillico) using semiempirical method of AM1. The first stage was molecules modelling of meperidine derivative compounds, followed with performing the process of geometric optimization. The second step was to determine the descriptor value in the form of electronic, steric, and hydrophobic descriptors. The last stage was done by statistics analysis using multiple regressions with backward model. The results showed that analgesic activity was significantly influenced by variation of descriptors, especially electronic descriptor which has more dominant influence than steric and hydrophobic descriptors. The most influential descriptor is the charge on N atoms, since N atoms are an important component in analgesic compounds.

Xanthine Oxidase Inhibition Activity and ADMET Properties of Terap (Artocarpus odoratissimus Blanco) Leaves Metabolites: Phytochemical Screening and in silico Studies

“…The higher the LogP value, the more lipophilic properties of the compound, or else, the compound is more non-polar. 28 If a compound is too non-polar, it can cause the compound to bind very tightly to the lipid membrane and make it difficult to get to the receptor. This is because, before binding to the receptor, the drug compound must pass through polar body fluids.…”

Qsar Analysis Using Semi-Empirical Am1 Method, Molecular Docking, and Admet Studies of Chalcone Derivatives as Antimalarial Compounds

“…Antimalarial activities of chalcone derivatives were examined by multilinear regression analysis using IBM ® SPSS ® software. This analysis aimed to assess the extent to which regression coefficients influence antimalarial activity (Utomo et al, 2017). The regression analysis generated seven QSAR equation models involving regression variables and antimalarial activity, as illustrated in Tables 3 and 4.…”

“…These include high R and R 2 values, which should exceed 0.8 (80%) and approach 1 (100%) to demonstrate a strong relationship between independent and dependent variables (Evita et al, 2022). A small standard error (SE) indicates the accuracy of the regression equation in predicting actual or true values (Utomo et al, 2017). A large Fcal/FTab value indicates a significant confidence level at the 95% level between physicochemical properties and antimalarial activity (Zain et al, 2020).…”

QSAR Modeling of Compounds Derived from 1,2,3-Triazolopiperidine as DPP-4 Enzyme Inhibitors Using Semiempirical AM1

“…QSAR (quantitative structure and activity relationship) has been designed to quantify a consistent relationship between molecular skeleton and its biological activity resulting an opportunity to evaluate the properties of new materials compared to a series of molecules being modeled [1,2]. The QSAR method can also allow chemists working in synthetic field to improve their desired products performance by modelling the molecules through appropriates approach [3,4].…”