وثيقة
Acetophenone-Based 3,4-Dihydropyrimidine-2(1H)-Thione as Potential Inhibitor of Tyrosinase and Ribonucleotide Reductase : Facile Synthesis, Crystal Structure, In-Vitro and In-Silico Investigations
وكيل مرتبط
Ejaz, Syeda Abida , مؤلف مشارك
Khalid, Aqsa, مؤلف مشارك
Channar, Pervaiz Ali, مؤلف مشارك
Aziz, Mubashir, مؤلف مشارك
Abbas, Qamar, مؤلف مشارك
Wani, Tanveer A., مؤلف مشارك
Alsaif, Nawaf A., مؤلف مشارك
Alanazi, Mashael G., مؤلف مشارك
Al-Hossaini, Abdullah M., مؤلف مشارك
عنوان الدورية
International Journal of Molecular Sciences
العدد
Volume 23 - Issue 21
دولة النشر
Bahrain
مكان النشر
Sakhir, Bahrain
الناشر
University of Bahrain
تاريخ النشر
2022
اللغة
إنجليزي
الموضوع
الملخص الإنجليزي
Abstract:
The acetophenone-based 3,4-dihydropyrimidine-2(1H)-thione was synthesized by the reaction of 4-methylpent-3-en-2-one (1), 4-acetyl aniline (2) and potassium thiocyanate. The spectroscopic analysis including: FTIR, 1H-NMR, and single crystal analysis proved the structure of synthesized compound (4), with the six-membered nonplanar ring in envelope conformation. In crystal structure, the intermolecular N–H ⋯ S and C–H ⋯ O hydrogen bonds link the molecule in a two-dimensional manner which is parallel to (010) the plane enclosing R22 (8) and R22 (10) ring motifs. After that, the Hirshfeld surfaces and their related two-dimensional fingerprint plots were used for thorough investigation of intermolecular interactions. According to Hirshfeld surface analysis, the most substantial contributions to the crystal packing are from H ⋯ H (59.5%), H ⋯ S/S ⋯ H (16.1%), and H ⋯ C/C ⋯ H (13.1%) interactions. The electronic properties and stability of the compound were investigated through density functional theory (DFT) studies using B3LYP functional and 6-31G* as a basis set. The compound 4 displayed the high chemical reactivity with chemical softness of 2.48. In comparison to the already reported known tyrosinase inhibitor, the newly synthesized derivatives exhibited almost seven-fold better inhibition of tyrosinase (IC50 = 1.97 μM), which was further supported by molecular docking studies. The compound 4 inside the active pocket of ribonucleotide reductase (RNR) exhibited a binding energy of −19.68 kJ/mol, and with mammalian deoxy ribonucleic acid (DNA) it acts as an effective DNA groove binder with a binding energy of −21.32 kJ/mol. The results suggested further exploration of this compound at molecular level to synthesize more potential leads for the treatment of cancer.
المجموعة
المعرف
https://digitalrepository.uob.edu.bh/id/b2af9cf3-1d96-41a6-81ac-6afda363903f
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