title: Investigation of the effects of some drugs and phenolic compounds on human dihydrofolate reductase activity.
abstract: Dihydrofolate reductase (DHFR) plays a fundamental role in cellular metabolism and cell growth. Inhibition of this enzyme will cause a decrease in the amount of folate that occurs in many metabolic processes, and the deficiency of which may cause various diseases. This study investigated the effects of some drugs and phenolic compounds on DHFR activity in vitro. To determine the inhibitory effect of compounds, enzyme activity was measured with a final concentration of an inhibitor ranging from 10 μM to 51 mM. DHFR was inhibited effectively by naringin, ferulic acid, and levofloxacin with IC50 values under 660 μM. Syringic acid, cefepime, ceftizoxime, cefazolin, ceftriaxone, and ceftazidime exhibited inhibitory effects on the enzyme activity with IC50 values in the range of 3.840-30.224 mM. K(i) constants were calculated using the Cheng-Prusoff equation. K(i) constants calculated in the range of 0.009-2.024 mM with respect to nicotinamide adenine dinucleotide phosphate oxidase (NADPH) and in the range of 0.060-5.830 mM about FH2.
authors.affiliation: Chemistry Department, Faculty of Science, Cankiri Karatekin University, Cankiri, Turkey. sevkiadem@gmail.com.
authors.forename: Erdem
authors.initials: E
authors.lastname: Aslan
authors.forename: Sevki
authors.initials: S
authors.lastname: Adem
mesh_terms: D002511:Cephalosporins / Q000494:pharmacology; D003373:Coumaric Acids / Q000494:pharmacology; D044950:Flavanones / Q000494:pharmacology; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D064704:Levofloxacin / Q000494:pharmacology; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism
chemical_list: D002511:Cephalosporins; D003373:Coumaric Acids; D044950:Flavanones; D005493:Folic Acid Antagonists; D005707:Gallic Acid; D064704:Levofloxacin; C004999:ferulic acid; C001945:syringic acid; D013762:Tetrahydrofolate Dehydrogenase; C005274:naringin
keywords: Drugs; Enzyme; Folate Deficiency; Inhibition; Natural Compounds