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Synthesis, cytotoxicity, pharmacokinetic profile, binding with DNA and BSA of new imidazo[1,2-a]pyrazine-benzo[d]imidazol-5-yl hybrids.
- Source :
-
Scientific Reports . 4/16/2020, Vol. 10 Issue 1, p1-14. 14p. - Publication Year :
- 2020
-
Abstract
- Novel derivatives possessing imidazo[1,2-a]pyrazine and 1H-benzo[d]imidazole scaffolds were synthesized using Suzuki-Miyaura cross-coupling reactions. In vitro anticancer activities against NCI-60 cancer cell panels were tested at 10 µM concentration. The best results were obtained from substitution of two 1-cyclohexyl-1H-benzo[d]imidazole groups present at C-6 and C-8 positions of imidazo[1,2-a]pyrazine (31). Compound 31 was found to be cytotoxic against 51 cell lines and cytostatic against 8 cell lines with broad range of growth inhibitions (−98.48 to 98.86%). GI50 value of compound 31 was found in the range of 0.80–2.87 µM for 59 human cancer cell lines at five-dose concentration levels. DNA binding study of potent compound 31 was suggested that this compound was intercalated into DNA base pairs with binding constant of 1.25 × 104 M−1. Compound 31 showed effective binding with bovine serum albumin (BSA) and presented binding constant value of 3.79 ×104 M-1. Pharmacokinetic studies revealed that all compounds are following Lipinski's rule of five and expected to be orally active. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PYRAZINES
*ANTINEOPLASTIC agents
*CANCER cells
*CELL lines
*SUZUKI reaction
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 10
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Scientific Reports
- Publication Type :
- Academic Journal
- Accession number :
- 142764171
- Full Text :
- https://doi.org/10.1038/s41598-020-63605-4