Naphtho[2,1-b]furan derived triazole-pyrimidines as highly potential InhA and Cytochrome c peroxidase inhibitors: Synthesis, DFT calculations, drug-likeness profile, molecular docking and dynamic studies

被引:19
作者
Roopa, D. L. [1 ]
Shyamsunder, K. [2 ]
Karunakar, Prashantha [3 ]
Rajabathar, Jothi Ramalingam [4 ]
Venkatesulu, Adavala [5 ]
Karnan, Muthusamy [6 ]
Kiran, K. S. [7 ]
Selvaraj, Manickam [8 ]
Basavarajaiah, S. M. [9 ]
机构
[1] NMKRV Coll Women, PG Dept Chem & Res Ctr, Jayanagar 3 Block, Bangalore 560011, Karnataka, India
[2] Indian Acad Degree Coll Autonomous, Dept Chem, Bengaluru 560043, Karnataka, India
[3] Visvesvaraya Technol Univ, Dept Biotechnol, Dayananda Sagar Coll Engn, Bangalore 560111, Karnataka, India
[4] King Saud Univ, Coll Sci, Dept Chem, POB 2455, Riyadh 11451, Saudi Arabia
[5] Govt First Grade Coll, Dept Postgrad Studies & Res Ctr Phys, Bangalore Rural 562114, Karnataka, India
[6] Rural Dev Adm, Natl Inst Anim Sci, Grassland & Forage Div, Chungcheongnam Do 31000, Cheonan, South Korea
[7] Jain Univ, Fac Engn & Technol, Dept Phys, Kanakapura Rd, Bangalore 562112, India
[8] Jiangsu Univ, Sch Chem & Chem Engn, Zhenjiang, Peoples R China
[9] Vijaya Coll, PG Dept Chem, Bengaluru 560004, Karnataka, India
关键词
ADME; DFT calculations; Molecular docking; Molecular dynamics; Naphtho-furan; Pyrimidine-triazine; SAR study; ANTIMICROBIAL ACTIVITY;
D O I
10.1016/j.molstruc.2023.135685
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
Napthofuran and its fused heterocyclic derivatives evaluated with varied biological activity functional groups comprise an important class of compounds for new chemical entities. We here in reporting synthesis of new 3-(4substituted phenyl)naphtho[1 ',2 ':4,5]furo[2,3-e][1,2,4]triazolo[4,3-c]pyrimidines 6(a-f). Structures of the newly synthesized compounds were confirmed by making use of spectroscopic techniques like IR, NMR and Mass. The DFT calculations were taken for the selected molecules using B3LYP hybrid functional with a 6-31+G (d, p) all-electron basis set using the Gaussian 09 package. The bioactivity predictions were evaluated for the synthesized compounds. The In vitro biological activities were reported for the all compounds 6(a-f). The compound 6a showed high activity of anti-TB and antioxidant activity with at MIC 1.6 mu g/ml and at percentage of inhibition (72.54 +/- 0.21) at 10 mu g/ml respectively. The compound 6f (73.21 +/- 0.11) showed antioxidant activity better than standard drug BHA (71.32 +/- 0.13) at 10 mu g/ml. Furthermore, the docking studies for the newly synthesized molecules were carried out by Auto dock software with proteins InhA (4TZK),Cytochrome c peroxidase (2 x 08) and protease (Mpro) of SARS-CoV-2 Omicron (PDB ID: 7TOB). All the compounds showed a strong binding affinity for the docked proteins. The outcome of docking results showed that compound 6ahad excellent binding energies -10.8, -9.4, and -9.0 kcal/mol with 4TZK, 2 x 08, and 7TOB respectively. Lastly, the protein stability, fluctuations of APO-Protein, protein-ligand complexes were investigated through Molecular Dynamics (MD) simulations studies using Desmond Maestro 11.3 and potential lead molecules were identified.
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页数:12
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