Indole bearing thiadiazole analogs: synthesis, β-glucuronidase inhibition and molecular docking study

被引：16

作者：

Almandil, Noor Barak ^{[1
]}

Taha, Muhammad ^{[1
]}

Gollapalli, Mohammed ^{[3
]}

Rahim, Fazal ^{[2
]}

Ibrahim, Mohamed ^{[1
]}

Mosaddik, Ashik ^{[1
]}

Anouar, El Hassane ^{[4
]}

机构：

[1] Imam Abdulrahman Bin Faisal Univ, IRMC, Dept Clin Pharm, POB 1982, Dammam 31441, Saudi Arabia

[2] Hazara Univ, Dept Chem, Mansehra 21300, Khyber Pakhtunk, Pakistan

[3] Imam Abdulrahman Bin Faisal Univ, Coll Comp Sci & Informat Technol, Dept Comp Informat Syst, POB 1982, Dammam 31441, Saudi Arabia

[4] Prince Sattam Bin Abdulaziz Univ, Coll Sci & Humanities, Dept Chem, POB 83, Al Kharj 11942, Saudi Arabia

来源：

BMC CHEMISTRY | 2019年 / 13卷 / 1期

关键词：

Synthesis; Indole; Thiadiazole; beta-Glucuronidases; Molecular docking; SAR; DEFICIENCY MUCOPOLYSACCHARIDOSIS; ANTICONVULSANT ACTIVITY; ANTIBACTERIAL ACTIVITY; BIOLOGICAL EVALUATION; FACILE SYNTHESIS; DERIVATIVES; BISINDOLYLMETHANE; ELUCIDATION; ANTICANCER; RECEPTOR;

D O I：

10.1186/s13065-019-0522-x

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Indole based thiadiazole derivatives (1-22) have synthesized, characterized by NMR and HREI-MS and evaluated for beta-Glucuronidase inhibition. All compounds showed outstanding beta-glucuronidase activity with IC50 values ranging between 0.5 +/- 0.08 to 38.9 +/- 0.8 A mu M when compared with standard d-saccharic acid 1,4 lactone (IC50 value of 48.1 +/- 1.2 A mu M). The compound 6, a 2,3-dihydroxy analog was found the most potent among the series with IC50 value 0.5 +/- 0.08 A mu M. Structure activity relationship has been established for all compounds. To confirm the binding interactions of these newly synthesized compounds, molecular docking study have been carried out which reveal that these compounds established stronger hydrogen bonding networks with active site residues.

引用

页数：10

共 45 条

[1] Synthesis and functionalization of Indoles through palladium-catalyzed reactions [J].

Cacchi, S ;

Fabrizi, G .

CHEMICAL REVIEWS, 2005, 105 (07) :2873-2920

[2] SUBSTITUTED 1,3,4-THIADIAZOLES WITH ANTICONVULSANT ACTIVITY .1. HYDRAZINES [J].

CHAPLEO, CB ;

MYERS, M ;

MYERS, PL ;

SAVILLE, JF ;

SMITH, ACB ;

STILLINGS, MR ;

TULLOCH, IF ;

WALTER, DS ;

WELBOURN, AP .

JOURNAL OF MEDICINAL CHEMISTRY, 1986, 29 (11) :2273-2280

[3] Facile synthesis, characterization and pharmacological activities of 3,6-disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles and 5,6-dihydro-3,6-disubstituted-1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles [J].

Chidananda, N. ;

Poojary, Boja ;

Sumangala, V. ;

Kumari, N. Suchetha ;

Shetty, Prashanth ;

Arulmoli, T. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2012, 51 :124-136

[4]

Dilipkumar U, 2018, ORG LETT, V20, P6336

[5] Design, Facile Synthesis, and Antibacterial Activity of Hybrid 1,3,4-thiadiazole-1,3,5-triazine Derivatives Tethered via -S- Bridge [J].

Dubey, Vaibhav ;

Pathak, Manish ;

Bhat, Hans R. ;

Singh, Udaya P. .

CHEMICAL BIOLOGY & DRUG DESIGN, 2012, 80 (04) :598-604

[6] Synthesis and in vitro leishmanicidal activity of 2-(5-nitro-2-furyl) and 2-(5-nitro-2-thienyl)-5-substituted-1,3,4-thiadiazoles [J].

Foroumadi, A ;

Pournourmohammadi, S ;

Soltani, F ;

Asgharian-Rezaee, M ;

Dabiri, S ;

Kharazmi, A ;

Shafiee, A .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (08) :1983-1985

[7]

GLASER JH, 1973, J LAB CLIN MED, V82, P969

[8] URINARY BETA-GLUCURONIDASE ACTIVITY IN RENAL-DISEASE [J].

GONICK, HC ;

KRAMER, HJ ;

SCHAPIRO, AE .

ARCHIVES OF INTERNAL MEDICINE, 1973, 132 (01) :63-69

[9] 1,5-dimethyl-6H-pyridazino[4,5-b]carbazole, a 3-aza bioisoster of the antitumor alkaloid olivacine [J].

Haider, N ;

Sotelo, E .

CHEMICAL & PHARMACEUTICAL BULLETIN, 2002, 50 (11) :1479-1483

[10] BETA-GLUCURONIDASE DEFICIENCY MUCOPOLYSACCHARIDOSIS - STUDIES IN CULTURED FIBROBLASTS [J].

HALL, CW ;

CANTZ, M ;

NEUFELD, EF .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1973, 155 (01) :32-38

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