Pyrazine based novel molecules as potential therapeutic agents: Synthesis, in vitro biological screening, in silico ADMET profiling and molecular docking study

被引:1
作者
Hussain, Rafaqat [1 ]
Hassan, Wagma [2 ]
Rahim, Fazal [3 ]
Subhan, Shazia [4 ]
Subhan, Zakia [5 ,6 ]
Khan, Shoaib [7 ]
Hussain, Amjad [8 ]
Ullah, Hayat [8 ]
Nabi, Muhammad [6 ]
Ullah, Riaz [9 ]
Ali, Essam A. [10 ]
Aghayeva, Saltanat [11 ]
机构
[1] Hunan Univ, Coll Biol, Changsha 410082, Hunan, Peoples R China
[2] COMSATS Univ, Inst Biotechnol, Abbottabad Campus, Abbottabad, Pakistan
[3] Hazara Univ, Dept Chem, Mansehra 21300, Pakistan
[4] Islamia Coll Peshawar, Dept Chem, Peshawar, Pakistan
[5] Khyber Med Univ, Inst Med Sci KMU IMS, Dept Pharmacol, Kohat, Pakistan
[6] Khyber Med Univ, Inst Pharmaceut Sci, Peshawar, Pakistan
[7] Abbottabad Univ Sci & Technol AUST, Dept Chem, Abbottabad, Pakistan
[8] Univ Okara, Inst Chem, Okara 56300, Pakistan
[9] King Saud Univ, Coll Pharm, Dept Pharmacognosy, Riyadh, Saudi Arabia
[10] King Saud Univ, Coll Pharm, Dept Pharmaceut Chem, Riyadh, Saudi Arabia
[11] Western Caspian Univ, Dept Polit Sci, Baku, Azerbaijan
关键词
Pyrazine; AChE; Anti-bacterial; Anti-fungal; Molecular docking; ADMET properties; ALZHEIMERS-DISEASE; ACETYLCHOLINESTERASE; BUTYRYLCHOLINESTERASE; ANALOGS; INHIBITORS; DONEPEZIL; DESIGN;
D O I
10.1016/j.rechem.2024.101698
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The current study described the synthesis of pyrazine-based novel molecules (1-15) using stepwise processes and their structures have been identified using various characterization techniques such as 1HNMR, 13CNMR, and HREI-MS. Furthermore, biological assessment of these scaffolds as anti-Alzheimer, anti-bacterial, and anti-fungal activities were evaluated. Their inhibitory potentials were determined using the minimum inhibitory concentration (MIC) in the presence of standard drugs donepezil (IC50 = 8.90 f 0.20 mu M), streptomycin (inhibition = 36.5 %), and Terbinafine (inhibition = 31.7 %) respectively. Among the screened molecules against acetylcholinesterase enzyme, the potent behavior was shown by scaffolds 1 (IC50 = 3.20 f 0.40 mu M), 2 (IC50 = 2.10 f 0.20 mu M), 4 (IC50 = 2.90 f 0.10 mu M), 5 (IC50 = 5.80 f 0.30 mu M), 6 (IC50 = 7.20 f 0.20 mu M), 8 (IC50 = 6.30 f 0.30 mu M), 9 (IC50 = 6.50 f 0.20 mu M), 10 (IC50 = 7.30 f 0.20 mu M) and 11 (IC50 = 7.10 f 0.20 mu M). Structureactivity relationship was carried out which mainly depends upon the substitution pattern around the phenyl ring. These compounds were further investigated by molecular docking studies which explore the binding interaction of ligands with active sites of enzymes. Moreover, ADMET prediction was also studied for potent scaffolds that displayed drug-like properties.
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页数:17
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