TPGS-mediated one-pot synthesis, XRD structural analysis, antimicrobial evaluation and molecular docking of novel heterocycles as potential inhibitors of p53-MDM2 protein

被引:7
作者
Anand, K. [1 ,2 ,3 ]
Naicker, Tricia [4 ]
Baijnath, Sooraj [4 ]
Mphahlele, Malose J. [5 ]
Katari, Naresh Kumar [6 ]
Zamisa, Sizwe J. [7 ]
Balakumar, C. [8 ]
Vijayakumar, K. [9 ]
Palanisamy, Subramanian [10 ]
Saravanan, Muthupandian [11 ]
Boomi, P. [12 ]
Chuturgoon, Anil [1 ]
机构
[1] Univ KwaZulu Natal, Sch Lab Med & Med Sci, Discipline Med Biochem, ZA-4001 Durban, South Africa
[2] Univ Free State, Fac Hlth Sci, Sch Pathol, Dept Chem Pathol, Bloemfontein, South Africa
[3] Univ Free State, Natl Hlth Lab Serv, Bloemfontein, South Africa
[4] Univ KwaZulu Natal, Catalysis & Peptide Res Unit, Durban, South Africa
[5] Univ South Africa, Coll Sci Engn & Technol, Dept Chem, Private Bag X6, ZA-1710 Florida, South Africa
[6] GITAM Deemed Be Univ, Dept Chem, Hyderabad 502329, Telangana, India
[7] Univ KwaZulu Natal, Sch Chem & Phys, Westville Campus,Private Bag X54001, ZA-4000 Durban, South Africa
[8] Philadelphia Univ, Fac Pharm, POB 1, Amman 19392, Jordan
[9] M Kumarasamy Coll Engn, Dept Chem, Karur 639113, Tamil Nadu, India
[10] Gangneung Wonju Natl Univ, East Coast Life Sci Inst, 120 Gangneung, Gangwon 210720, South Korea
[11] Mekelle Univ, Coll Hlth Sci, Sch Med, Dept Microbiol & Immunol,Div Biomed Sci, Mekelle 1871, Ethiopia
[12] Alagappa Univ, Dept Bioinformat, Karaikkudi 630003, Tamil Nadu, India
基金
新加坡国家研究基金会;
关键词
XRD; Molecular docking; TPGS; One-pot synthesis; p53-MDM2; protein; CHEMISTRY;
D O I
10.1016/j.molstruc.2019.127252
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
Novel heterocyclic bioactive small molecules bearing thioether moiety, fluorine containing dihydro pyridine and dihydro pyran were synthesized and characterized using spectroscopic methods (FT-IR, H-1, C-13 and F-19 NMR), LC-MS and SC-XRD. The reaction conducted is highly environment-friendly involving D-alpha-Tocopherol polyethylene glycol succinate (TPGS) - Water binary solvent as reaction medium. All of the synthesized final compounds were evaluated against 2 g-negative [Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853)] and 1 g-positive [Staphylococcus aureus (ATCC 29213)] bacterial strains by in vitro. Molecular docking experiments were carried out against p53-MDM2 tumor suppressor protein to gain more insights into the binding mode of the final compounds. In this study, we discovered potent p53-MDM2 inhibition by 2-thiobenzyl-3-formyl quinoline, 2-thio-1,2-dihydroquinoline-3-formyl N-substituted thiosemi-carbazone and fluorine substituted new pyridine and pyran derivatives by structure-based design. (C) 2019 Elsevier B.V. All rights reserved.
引用
收藏
页数:9
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