Synthesis and Biological Activities of Distamicin A Analogues

Distamycin A is a natural product possessing amide group and three N-methyl pyrrole rings terminated with neutral formamide and positively charged propylamidinium. It has been discovered and investigated as DNA minor groove binder, it acts as anti bacterial agent. Distamycin A binds to the minor groove of double- stranded DNA at Adinine-Thymine rich regions by forming hydrogen bond and hydrophobic interaction. Terminal amidine group of molecule is basic and have positive charge, this serve the molecule to be attracted to negatively charged DNA phosphodiester backbone. DNA is changed when it is bind with distamycin A. This is recognized from the chemical structure of minor groove. Distamycin A analogues have been synthesized to increase its binding with minor groove. In this research a new distamycin A analogues were synthesized by changing N-terminal alkyl group which have lower molecular weight and higher lipophilicity than previous analogues .This will increase the binding with minor groove, and may increase biological activity as anti cancer, in addition to its anti bacterial activity. We have synthesized five new analogues of Distamycin A in this research, the synthesized analogues were characterized by1HNMR, 13 C NMR and IR. Synthesized compounds were tested for antioxidant ,antibacterial and antifungal activities. According to antibacterial activities the most active one was N-(1-Methyl-5-(2-(4-sulfamoyl-phenyl)-ethylcarbamoyl)-1H-pyrrol-3-yl)-nicotinamide and Methanesulfonic acid 4-(2-((4-benzoylamino-1-methyl-1H-pyrrole-2-carbonyl)amino)-ethyl)-phynel ester. They reveled about 10% of Gentamicin, whihl 4-benzoylamino-1-methyl-1H-pyrrole-2-carboxylic acid (3-dimethylamino-propyl)-amide revealed the highest activity against Microsproum Canis (72% inhibition).