1-(1-(4-hidroksibütil)-6-metil-4-fenil-2-tioksoheksahidropirimidin-5-il)etan-1-on Bileşiğinin Moleküler Doking, ADME Analiz ve DFT Yöntemi ile Teorik Hesaplamalar

Year 2025, Volume: 8 Issue: 3, 1129 - 1145, 16.06.2025

Efdal Çimen , Kenan Gören , Veysel Tahiroğlu , Ümit Yıldıko

https://doi.org/10.47495/okufbed.1562370

Abstract

Gaussian 09W yazılımı kullanılarak, 1-(1-(4-hidroksibutil)-6-metil-4-fenil-2-tioksohekzahidropirimidin-5-il)etan-1-one (HMEP) bileşiğinin teorik olarak ideal moleküler yapısı incelenmiştir. Bileşiğin moleküler yapısı ve kimyasal reaktivitesi, Yoğunluk Fonksiyonel Teorisi (DFT) kullanılarak araştırıldı. Kuantum kimyasal hesaplamaları, temel kümeler ve DFT(B3LYP/6-311G(d,p) ve DFT(B3LYP/LANL2DZ) yaklaşımı kullanılarak yapıldı. HMEP molekülünün reaktif alanlarını belirlemek amacıyla moleküler elektrostatik potansiyel (MEPS) haritaları oluşturuldu. Moleküler yük aktarımı için HOMO ve LUMO analizleri yapıldı. Molekülün stabilitesi, NBO analizi kullanılarak yük delokalizasyonu ve hiperkonjugatif etkileşimin bir fonksiyonu olarak incelenmiştir. Moleküler optimizasyon her iki yaklaşımda da aynı metot ve temel setlerle gerçekleştirildi. Çalışmanın devamında HMEP molekülünün moleküler analizi yapıldı. Emilim, dağılım ve metabolizma için uygun değerleri gösteren bileşiklerin ADME profilini tahmin etmek için SwissADME araçları kullanıldı. Bu araştırmanın sonuçları güvenli ve etkili bir farmakolojik ilaç üreten endüstride faydalı olabileceğini göstermektedir.

Keywords

DFT , Moleküler Doking , MEP , ADME , NBO

The Theoretical Calculations by DFT Method and Analysis ADME, Molecular Docking of 1-(1-(4-hydroxybutyl)-6-methyl-4-phenyl-2-thioxohexahydropyrimidin-5-yl)ethan-1-one (pyrimidine-thiones) Compound

Abstract

Using Gaussian 09W software, the theoretically ideal molecular structure of 1-(1-(4-hydroxybutyl)-6-methyl-4-phenyl-2-thioxohexahydropyrimidin-5-yl)ethan-1-one (HMEP) compound was investigated. We investigated the compound's chemical reactivity and molecular structure using Density Functional Theory (DFT). Quantum chemical calculations were performed using DFT(B3LYP/6-311G(d,p) and DFT(B3LYP/LANL2DZ) basis sets and approaches. The reactive sites of the HMEP molecule were determined by creating molecular electrostatic potential (MEPS) maps. In order to investigate molecular charge transfer, HOMO and LUMO analyses were done. Through the use of NBO analysis, the stability of the molecule was examined in relation to charge hyperconjugative and delocalization interactions. In both cases, the same methodology and basis sets were used for molecular optimization. In continuation of the study, molecular analysis of the HMEP molecule was performed. SwissADME tools were used to predict the ADME profile of compounds showing appropriate values for absorption, distribution and metabolism. The results of this research indicate that it can be useful in the industry producing safe and effective pharmaceutical drugs.

Keywords

DFT , Moleküler Docking , MEP , ADME , NBO

References

• Abdullah A., Tanriverdi AA., Khan AA., Lee SJ., Park JB., Kim YS., Yildiko U., Min K., Alam M. Selenium-substituted conjugated small molecule: Synthesis, spectroscopic, computational studies, antioxidant activity, and molecular docking. Journal of Molecular Structure 2024; 1304: 137694.
• Alghamdi S., Abbas F., Hussein R., Alhamzani A., El‐Shamy N. Spectroscopic characterization (IR, UV-Vis), and HOMO-LUMO, MEP, NLO, NBO analysis and the antifungal activity for 4-bromo-N-(2-nitrophenyl) benzamide; using DFT modeling and In silico molecular docking. Journal of Molecular Structure 2023; 1271: 134001.
• Bağlan M., Gören K., Çakmak İ. Theoretical investigation of 1H and 13C NMR Spectra of diethanol Amine dithiocarbamate RAFT agent. Journal of the Institute of Science and Technology 2022; 12(3): 1677-1689.
• Bağlan M., Gören K., Yıldıko Ü. DFT computations and molecular docking studies of 3-(6-(3-aminophenyl)thiazolo[1,2,4]triazol-2-yl)-2H-chromen-2-one(ATTC) molecule. Hittite Journal of Science and Engineering 2023a; 10(1): 11-19.
• Bağlan M., Gören K., Yıldıko Ü. HOMO–LUMO, NBO, NLO, MEP analysis and molecular docking using DFT calculations in DFPA molecule. International Journal of Chemistry and Technology 2023b; 7(1): 38-47.
• Bağlan M., Yıldıko Ü., Gören K. Computational investigation of 5.5'',7''-trihydroxy-3,7-dimethoxy-4'-4'''-O-biflavone from flavonoids using DFT calculations and molecular docking. Adıyaman University Journal of Science 2022; 12(2): 283-298.
• Bağlan M., Yıldıko Ü., Gören K. DFT calculations and molecular docking study in 6-(2”-pyrrolıdınone-5”-Yl)-(-) epicatechın molecule from flavonoids. Eskişehir Teknik Üniversitesi Bilim ve Teknoloji Dergisi B - Teorik Bilimler 2023; 11(1): 43-55.
• Chagas CM., Moss S., Alisaraie L. Drug metabolites and their effects on the development of adverse reactions: revisiting lipinski’s rule of five. International Journal of Pharmaceutics 2018; 549(1): 133-149.
• Chen X., Li H., Tian L., Li Q., Luo J., Zhang Y. Analysis of the physicochemical properties of acaricides based on lipinski's rule of five. Journal of Computational Biology 2020; 27(9): 1397-1406.
• Dinakaran VS., Jacob D., Mathew JE. Synthesis and biological evaluation of novel pyrimidine-2(1H)-ones/thiones as potent anti-inflammatory and anticancer agents. Medicinal Chemistry Research 2012; 21(11): 3598-3606.
• Gören K., Bağlan M., Tahiroğlu V., Yıldıko Ü. Theoretical calculations and molecular docking analysis of 4-(2-(4-bromophenyl)hydrazineylidene)-3,5-diphenyl-4H-pyrazole molecule. Journal of Advanced Research in Natural and Applied Sciences 2024; 10(4): 786-802.
• Gören K., Bağlan M., Yıldıko Ü. Antimicrobial, and antitubercular evaluation with adme and molecular docking studies and dft calculatıons of (z)-3-((1-(5-amino-1,3,4-thiadiazol-2-yl)-2-phenylethyl)imino)-5-nitroindolin-2-one schiff base. Karadeniz Fen Bilimleri Dergisi 2024a; 14(4): 1694-1708.
• Gören K., Bağlan M., Yıldıko Ü. Melanoma cancer evaluation with adme and molecular docking analysis, Dft calculations of (e)-methyl 3-(1-(4-methoxybenzyl)-2,3-dioxoindolin-5-yl)-acrylate molecule. Journal of the Institute of Science and Technology 2024b; 14(3): 1186-1199.
• Gören K., Yıldıko Ü. Aldose reductase evaluation against diabetic complications using ADME and molecular docking studies and DFT calculations of spiroindoline derivative molecule. Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi 2024; 28(2): 281-292.
• Gularte MS., Anghinoni JM., Abenante L., Voss GT., de Oliveira RL., Vaucher RA., Luchese C., Wilhelm EA., Lenardão EJ., Fajardo AR. Synthesis of chitosan derivatives with organoselenium and organosulfur compounds: characterization, antimicrobial properties and application as biomaterials. Carbohydrate Polymers 2019; 219: 240-250.
• Kartal B., Tanriverdi AA., Yildiko U., Tekes AT., Çakmak I. Polyimide synthesis and characterizations: DFT-assisted computational studies on structural units. Iranian Polymer Journal 2024: 1-23.
• Kassel DB. Applications of high-throughput ADME in drug discovery. Current Opinion in Chemical Biology 2004; 8(3): 339-345.
• Khodja IA., Boulebd H., Bensouici C., Belfaitah A. Design, synthesis, biological evaluation, molecular docking, DFT calculations and in silico ADME analysis of (benz) imidazole-hydrazone derivatives as promising antioxidant, antifungal, and anti-acetylcholinesterase agents. Journal of Molecular Structure 2020; 1218: 128527.
• Mustafa M., Zreid MS., Abadlehb MM. One-pot synthesis of model 1H, 1'H-5, 5'-Bi (1, 2, 4-triazoles). Heterocycles 2018; 96(6): 1080-1087.
• Nogara PA., Saraiva RdA., Caeran Bueno D., Lissner LJ., Lenz Dalla Corte C., Braga MM., Rosemberg DB., Rocha JBT. Virtual screening of acetylcholinesterase inhibitors using the lipinski’s rule of five and zinc databank. BioMed Research International 2015; 2015(1): 870389.
• Suvitha A., Periandy S., Gayathri P. NBO, HOMO–LUMO, UV, NLO, NMR and vibrational analysis of veratrole using FT-IR, FT-Raman, FT-NMR spectra and HF–DFT computational methods. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2015; 138: 357-369.
• Tahiroğlu V., Çimen E. 3-[1-(5-Amino-[1,3,4]tiadiazol-2-il)-2-(1H-imidazol-4-il)-etilimino]-2,3-dihidro-indol-2-on molekülün teoriksel incelenmesi. Türk Doğa ve Fen Dergisi 2024; 13(2): 6-13.
• Tahiroğlu V., Gören K., Bağlan M., Yıldıko Ü. Molecular docking and DFT analysis of thiazolidinone-bis schiff base for anti-cancer and anti-urease activity. Journal of the Institute of Science and Technology 2024; 14(2): 822-834.
• Tahiroğlu V., Gören K., Çimen E., Yıldıko Ü. Moleculer docking and theoretical analysis of the (E)-5-((z)-4-methylbenzylidene)-2-(((e)-4-methylbenzylidene)hydrazineylidene)-3-phenylthiazolidin-4-one molecule. Bitlis Eren Üniversitesi Fen Bilimleri Dergisi 2024; 13(3): 659-672.
• Tahiroğlu V., Gören K., Yıldıko Ü., Bağlan M. IInvestigation, structural characterization and evaluation of the biological potency by molecular docking of amoxicillin analogue of a schiff base molecule. International Journal of Chemistry and Technology 2024; 8(2): 190-199.
• Taslimi P., Sujayev A., Turkan F., Garibov E., Huyut Z., Farzaliyev V., Mamedova S., Gulçin İ. Synthesis and investigation of the conversion reactions of pyrimidine‐thiones with nucleophilic reagent and evaluation of their acetylcholinesterase, carbonic anhydrase inhibition, and antioxidant activities. Journal of Biochemical and Molecular Toxicology 2018; 32(2): e22019.
• Yildiko U., Tanriverdi AA. Synthesis and characterization of pyromellitic dianhydride based sulfonated polyimide: survey of structure properties with DFT and QTAIM. Journal of Polymer Research 2021; 29(1): 19.
• Yildiko U., Tanriverdi AA. A novel sulfonated aromatic polyimide synthesis and characterization: Energy calculations, QTAIM simulation study of the hydrated structure of one unit. Bulletin of the Korean Chemical Society 2022; 43(6): 822-835.
• Yildiko Ü., Türkan F., Tanriverdi AA., Ata AC., Atalar MN., Cakmak İ. Synthesis, enzymes inhibitory properties and characterization of 2- (bis (4-aminophenyl) methyl) butan-1-ol compound: Quantum simulations, and in-silico molecular docking studies. Journal of the Indian Chemical Society 2021; 98(11): 100206.
• Yu J., Jiang X. Synthesis and perspective of organosulfur chemicals in agrochemicals. Advanced Agrochem 2023; 2(1): 3-14.