Synthesis, Structural Characterization, and Antioxidant Activities of 2,4-Dinitrophenyl-Hydrazone Derivatives

Byline: Ghulam Ahad, Momin Khan, Asif Khan, Mohammad Ibrahim, Uzma Salar, Kanwal, Khalid Mohammed Khan and Shahnaz Perveen

Summary: Thirty-two derivatives of 2,4-dinitro phenylhydrazone 1-32 were synthesized by one step reaction and characterized by spectroscopic techniques such as EI-MS and 1H-NMR. Compounds 1-32 were screened for their in vitro antioxidant activities. DPPH radical scavenging, ferrous ion-chelating, ferric ion reducing, total antioxidants, and hydroxyl radical scavenging assays were used to check the antioxidant potential of the synthetic derivatives. Compounds showed good to moderate antioxidant activities as compared to the standard vitamin C (for DPPH radical scavenging (IC50 = 77.83 +- 16.56 uM), ferric ion reducing (IC50 = 92.16 +- 17.74 uM), total antioxidant (IC50 = 97.85 +- 17.21 uM), and hydroxyl radical scavenging (IC50 = 96.128 +- 17.50 uM) activities) and EDTA (for ferrous ion-chelating assay (IC50 = 101.86 +- 17.84 uM)). This study has identified potential leads for future research on antioxidant agents of this class of compounds.

Keywords: Schiff bases; 2,4-dinitro-phenyl hydrazone; Reactive oxygen species; Antioxidant; In vitro.

Introduction

Schiff bases are condensation products of primary amines and carbonyl compounds, possesses oxygen and nitrogen donor atoms, and represented by general formula R2R3C=NR1 [1,2]. Schiff bases were first time discovered by German Scientist, Hugo Schiff in 1864 [2]. Schiff bases are also known as imine or azomethine which are the nitrogen analogue of an aldehydes or ketones in which the carbonyl group is replaced by an imine or azomethine group [3,4]. Imine or azomethine groups are existing in different natural, naturally derived and non-natural compounds. Imine containing compounds have been displayed a wide range of biological activities [5, 6]. In organic synthesis the formation of carbon-nitrogen double bond is of great interest and can be achieved in acidic medium by the reaction of aldehydes/ketones and amines [7, 8]. Similarly, in pharmaceutical and medicinal field, Schiff bases are playing an important role [9].

Such class of compounds displayed various biological activities such as antibacterial, a ntifungal, antitumor and antiherbicidal activities etc. [10]. Antioxidants are the agents which prevent blood vessel membranes from oxidative damage thus ensure proper blood circulation and avoid cardiovascular diseases. They provide defense against cancer-causing DNA damages. Modes of action of antioxidants are attributed to their radical scavenging activity by contributing one electron to the free radicals and to convert them into harmless molecules. Antioxidants thus protect cells from the oxidative damage that leads to aging and other diseases [11-13]. Proteins, nucleic acids, lipids, and extra-cellular matrix glycosaminoglycans (e.g. hyaluronic acid) are found to have strong affinity for free radicals and cause different diseases. The polyunsaturated fatty acids are more vulnerable to free radical damage, causing cerebral ischemia and other CNS diseases [14].

Free radicals have also been found to contribute in the pathology of arteriosclerosis, malaria and rheumatoid arthritis, in neurodegenerative disease, and aging [15,16]. Thus, the discovery and development of effective antioxidants, capable of supplementing body's antioxidant system is an important area of research. Our group has discovered a variety of Schiff bases for their antioxidant...