SwissADME studies and Density Functional Theory (DFT) approaches of methyl substituted curcumin derivatives

Afridi M. B., Sardar H., SERDAROĞLU G., Shah S. W. A., Alsharif K. F., Khan H.

Computational Biology and Chemistry, cilt.112, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 112
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1016/j.compbiolchem.2024.108153
  • Dergi Adı: Computational Biology and Chemistry
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Applied Science & Technology Source, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, Chimica, Compendex, Computer & Applied Sciences, EMBASE, INSPEC, MEDLINE, zbMATH
  • Anahtar Kelimeler: Curcumin Derivatives, DFT studies, pharmacokinetic properties, SwissADME
  • Sivas Cumhuriyet Üniversitesi Adresli: Evet

Özet

Research suggests curcumin's safety and efficacy, prompting interest in its use for treating and preventing various human diseases. The current study aimed to predict drag ability of methyl substituted curcumin derivatives (BL1 to BL4) using SwissADME and Density Functional Theory (DFT) approaches. The curcumin derivatives investigated mostly adhere to Lipinski's rule of five, with molecular properties including MW, F. Csp3, nHBA, nHBD, and TPSA falling within acceptable limits. The compounds demonstrating high lipophilicity while poor water solubility. The pharmacokinetic evaluation revealed favorable gastrointestinal absorption and blood-brain barrier permeation while none were identified as substrates for P-glycoprotein, however, revealed inhibitory actions against various cytochrome P450 enzymes. Additionally, all derivatives exhibited a consistent bioavailability score of 0.55. Similarly, the DFT computations of the compounds of the curcumin derivatives were conducted at B3LYP/6–311 G** level to predict and then assess the key electronic characteristics underlying the bioactivity. Accordingly, the BL4 molecule (ΔEgap= 4.105 eV) would prefer to interact with the external molecular system more than the other molecules due to having the biggest energy gap. The ΔNmax (2.328 eV) and Δεback-donat. (-0.446 eV) scores implied that BL1 would have more charge transfer capability and the lowest stability via back donation among the compounds. In short, the derivative (BL1 to BL4) exhibited strong extrinsic therapeutic properties and therefore stand eligible for further in vitro and in vivo studies.