Interesting coordination abilities of antiulcer drug famotidine and antimicrobial activity of drug and its cobalt(III) complex.
Crystal structure of a novel cobalt(III) complex with antiulcer drug famotidine and ethylenediamine was determined. This is the second structure of a transition metal complex with famotidine resolved by a single crystal X-ray analysis, in which famotidine shows different mode of coordination than that observed in the other cases. Drug molecule is coordinated to metal ion as a tetradentate ligand through guanidine N6, thiazole N4, thioether S2 and terminal N3 atom. Two NH(2) groups (N3H(2) and N6H(2)) are deprotonated and drug coordinates as dianion. In the asymmetric unit, one chloride anion and one water molecule were found to complete the complex stoichiometry. The structure of the complex is abundant in atoms, which can be involved in hydrogen bond formation either as hydrogen acceptors or hydrogen donors. Because of that, a great number of hydrogen bonds dominates the crystal packing. Beside the hydrogen bonds, there are two interesting noncovalent interactions: CH(...)pi and NH(...)pi within the famotidine anion, which stabilize the complex structure. The pi(...)pi stacking interactions between neighboring complex cations are also observed. Antibacterial and antifungal activity of famotidine and its newly synthesized complex against representative bacteria: Escherichia coli, Staphilococcus aureus and Micrococcus lysodeikticus and fungi: Aspergillus niger and Candida albicans were examined. The results indicate a higher selectivity of the famotidine-Co(III) complex, as well as better growth inhibitory activity (lower MIC values (MIC, minimal inhibitory concentration)) in comparison with the drug alone.
Miodragović
Djenana U
DU
Faculty of Chemistry, University of Belgrade, Studentski trg 16, P.O. Box 158, 11 000 Belgrade, Serbia and Montenegro. dmiodrag@chem.bg.ac.yu
Bogdanović
Goran A
GA
Miodragović
Zoran M
ZM
Radulović
Milanka D
MD
Novaković
Sladjana B
SB
Kaluderović
Goran N
GN
Kozłowski
Henryk
H
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry*; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis / Q000737:chemistry*; D003035:Cobalt / Q000737:chemistry*; D003300:Copper / Q000737:chemistry; D003460:Crystallization; D018360:Crystallography, X-Ray; D015738:Famotidine / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D009942:Organometallic Compounds; D003035:Cobalt; D015738:Famotidine; D003300:Copper