Molecular docking and spectroscopic studies of sulfonamide-based imines with human serum albumin

  • سال انتشار: 1400
  • محل انتشار: اولین همایش بین المللی و دهمین همایش ملی بیوانفورماتیک ایران
  • کد COI اختصاصی: IBIS10_171
  • زبان مقاله: انگلیسی
  • تعداد مشاهده: 187
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نویسندگان

Baran Mohamadi Moghadam

Department of Chemistry, College of Science, University of Tehran, Tehran, Iran

Aria Tajalli

Department of Chemistry, College of Science, University of Tehran, Tehran, Iran

Ahmad Amiri

Department of Chemistry, College of Science, University of Tehran, Tehran, Iran

چکیده

Human serum albumin contains about ۶۰% of the total plasma protein and commonly used to study drugproteininteractions. HSA shows high affinity to different drugs, nutrients, metal ions, and their metabolites.Based on materials’ affinity to HSA, their absorption, distribution, metabolism, and toxicity could be changedin vivo and then affect their pharmacokinetics, pharmacodynamics, and toxicity. Sulfonamides are animportant class of antibiotics, which have been widely used as feed additives in agriculture for decades.Wereport here, the synthesis of two sulfonamide ligands, SulfHB and SulfTP. The chemical structure of theligands were dtetermined by different spectroscopic techniques. The binding modes of SulfHB and SulfTPligands with HSA was explored experimentally and computationally. The fluorescence titration experimentrevealed a strong complex formation between the ligands and HSA, with a significant quenching by a blueshift of ~۱۸ nm at the λ max of ۳۴۳.The molecular docking approaches revealed that SulfHB or SulfTP couldspontaneously enter into the binding sites of HSA through H-bond interactions and van der Waals forces,and that SulfHB exhibited much stronger binding affinity toward HSA than SulfTP at different temperatures(ΔG =-۱۱.۲۹ for SulfHB, and ΔG = -۹.۵۲ for SulfTP). The binding constants for SulfTP-HSA weredetermined to be ۳۹.۹۵ × ۱۰ ۵ L.mol −۱ at ۲۹۸ K., and SulfHB had a greater effect on the α-helix content ofHSA. Observations from molecular docking studies revealed that the hydrogen bonds might be a key factorcontributing to the binding affinity of sulfa drugs and HSA. The aminoacids such as Arg۱۱۷, Asn۱۳۰,Asp۱۲۹, Lys۱۹۹, Ala ۲۹۷ and Arg۲۲۲, play key roles in the sulfonamide-HSA binding process via theirinteraction with the sulfone (O=S=O) and hydroxyl groups of the ligands. These findings might be helpful tounderstand the biological effects of sulfonamides in humans.

کلیدواژه ها

HSA; Sulfa Drugs; Molecular Docking; DFT-BPV۸۶; GAUSSIAN; Sulfadiazine

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