2-(4-Klorobenzil)-6-(4-metoksifenil)imidazo[2,1-b][1,3,4]tiadiazol’un DFT Hesaplamaları, ADME Çalışmaları ve Moleküler Doking ile in-silico İlaç Değerlendirmesi

Year 2025, Volume: 12 Issue: 2, 504 - 520, 30.11.2025

Kenan Gören , Mehmet Bağlan , Veysel Tahiroğlu , Ümit Yıldıko

https://doi.org/10.35193/bseufbd.1632642

Abstract

İmidazo[2,1-b][1,3,4]tiadiazol heterosiklünün keşfi 1950'lerde görüldü. İmidazo[2,1-b][1,3,4]tiadiazol türevlerinin antibakteriyel, antifungal, antikonvülsan, analjezik, antikanser, antiinflamatuar, diüretik ve anestezik olarak farmakolojik potansiyeli kapsamlı bir şekilde incelenmiştir. Mevcut araştırma, 2-(4-Klorobenzil)-6-(4-metoksifenil)imidazo[2,1-b][1,3,4]tiadiazol (CMT) bileşiğini Gaussian 09 yazılım programı ile teorik olarak incelemektir. Bahsedilen bileşiğin teorik hesaplamaları, popüler yoğunluk fonksiyonel teorisi (DFT) teorileri B3LYP, MPW1PW91 metotlar 6-311G(d,p) temel set kullanılarak yapılmıştır. Optimize edilmiş yapının en yüksek dolu moleküler orbitali (HOMO), en düşük boş moleküler orbitali LUMO, doğal bağ orbitali NBO, doğrusal olmayan optik (NLO), moleküler elektrostatik potansiyeli (MEP), ve Mulliken yükleri aynı temel set ve farklı metotlar teorik olarak hesaplandı ve elde edilen değerler birbirleriyle kıyaslandı. Ek olarak, CMT bileşiğinin bir ilaç olarak değerlendirilmesi için emilim, dağılım, metabolizma, atılım ve toksisite (ADME) profillerini tahmin etmek için in silico çalışmalar yürütülmüştür. ADME çalışmasına dayanarak, bileşiğin iyi bir potansiyel ilaç benzeri karaktere sahip olacağına inanıyoruz. Son olarak, 3PP0 ve 1M17 enzimleri PDB'den (Protein Veri Bankası) indirildi ve CMT bileşiğinin meme kanseri üzerindeki potansiyeli moleküler doking analizi ile in silico olarak hesaplandı. Doking analizi sonucununa göre, CMT bileşiğinin doking skoru sırasıyla -10.20 ve -7.20 kcal/mol olarak elde edildi. Doking analizinde, meme kanseri hakkındaki teorik verilerin gözlenen değerlerle iyi bir şekilde ilişkili olduğu gösterildi.

Keywords

Moleküler Doking , MEP , DFT , NBO , ADME

In-silico Drug Evaluation by Molecular Docking and ADME Studies, DFT Calculations of 2-(4-Chlorobenzyl)-6-(4-methoxyphenyl)imidazo [2,1-b][1,3,4]thiadiazole

Abstract

The discovery of the imidazo[2,1-b][1,3,4]thiadiazole heterocycle was seen in the 1950s. The pharmacological potential of imidazo[2,1-b][1,3,4]thiadiazole derivatives as antibacterial, antifungal, anticonvulsant, anticancer, analgesic, anti-inflammatory, diuretic, and anesthetic has been extensively studied. The present investigation is to examine the 2-(4-Chlorobenzyl)-6-(4-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazole (CMT) compound theoretically with the Gaussian 09 software program. The mentioned compound’s theoretical calculations were done on using the popular density functional theory (DFT) theories B3LYP, MPW1PW91 methods, the 6-311G(d,p) basis set. The highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital LUMO, natural bonding orbital NBO, nonlinear optical (NLO), molecular electrostatic potential (MEP), and Mulliken charges of the optimized structure were calculated theoretically with the same basis set and different methods, and the obtained values were compared with each other. Additionally, in silico studies were conducted to estimate the absorption, distribution, metabolism, excretion and toxicity (ADME) profiles of CMT compound to evaluate it as a drug. Based on the ADME study, we believe that the compound will have good potential drug-like character. Finally, 3PP0 and 1M17 enzymes were downloaded from PDB (Protein Data Bank) and the potential of CMT compound on breast cancer was calculated in silico by molecular docking analysis. According to the docking analysis outcomes, the docking score of CMT compound was obtained as -10.20 and -7.50 kcal/mol, respectively. In the docking analysis, it was shown that the theoretical data on breast cancer were well correlated with the observed values.

Keywords

Molecular Docking , DFT , NBO , MEP , ADME

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