Synthesis & Characterization of N-methylpyrrole Containing Distamycin A Analogues Which Have Potential Biological Activity
Date
2017-05-23
Authors
عمر, براءه
Journal Title
Journal ISSN
Volume Title
Publisher
An-Najah National University
Abstract
A new set of Distamycin A analogues have been synthesized to improve their binding with minor groove by changing molecular masses and lipophilicity with the N-terminal alkyl group. This may increase biological activity as anti-cancer, in addition to its anti-bacterial activity. The compounds are N(5((3(dimethylamino) propyl) carbamoyl)-1-methyl-1H-pyrrol-3-yl)
nicotinamide (B1), 4-benzamido-N-(3-(dimethylamino)propyl)-1-methyl-1H-pyrrole-2-carboxamide(B2), 4-acetamido-N-(3(dimethylamino)propyl)-1-methyl-1H-pyrrole-2-carboxamide(B3), N-(5-((5-((3-(dimethylamino) propyl) carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl) nicotinamide(B4),4-benzamido-N-(5-((3-(dimethylamino)propyl) carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide (B5), 4-acetamido-N-(5-((3-(dimethylamino)propyl)carbamoyl)-1-methyl-1H-pyrrole-3-yl)-1-methyl-1H-pyrrole-2-carboxamide(B6),4-benzamido-N-(5((5-((3-(dimethylamino)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrole-3-yl)-1-methyl-1H-pyrrole-2-carboxamide(B7), 4-benzamido-N-(3-((3-(dimethylamino) propyl) carbamoyl) phenyl)- 1-methyl-1H-pyrrole-2-carboxamide(B8), 4-benzamido-N-(5-((3-((3-(dimethylamino)
propyl)carbamoyl)phenyl)carbamoyl)-1-methyl-1H-pyrrole-3-yl)-1-methyl-1H-pyrrole-2-carboxamide(B9), N-(5-((5-((3-((3-(dimethylamino)propyl)
carbamoyl)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)picolinamide(B10), 4-benzamido-1-methyl-N-(1-
methyl-5-((2-morpholinoethyl)carbamoyl)-1H-pyrrol-3-yl)-1H-pyrrole-2-carboxamide(B11), 4-benzamido-1- methyl-N- (1-methyl-5-((1-methyl-5-((2-morpholinoethyl)carbamoyl)-1H-pyrrol-3-yl)carbamoyl)-1H-pyrrol-3-yl)-1H- pyrrole-2- carboxamide (B12), N-(1-methyl-5- ((1-methyl-5- ((1-methyl-5-((2-morpholinoethyl)carbamoyl)-1H-pyrrol-3-yl)carbamoyl)-1H-pyrrol-3-yl)carbamoyl)-1H-pyrrol-3-yl)nicotinamide(B13), using acceptable methods shown in the experimental part. The structures of those compounds were confirmed by Fourier Transform Infrared (FT-IR), and Proton Nuclear Magnetic Resonance (1H-NMR). Although the compounds didn’t show significant activity as antioxidants, but (B3 and B13) have reductive potential activity (601.8 and 277.2 respectively) compared with (Gallic acid=470.7). On the other hand, they showed antifungal activity against the tested dematophytes. B6 and B8 revealed 100% inhibition against T. rubrurm CBS 392.58 and more than 80% against the other type’s fungi at the concentration 240µg/ml .