Ulcer Index, Analgesics and Anti inflammatory Screening of Some Arylidene Compounds Derived from Phenyl Hydrazine and Aromatic Aldehydes

Research Article

Austin J Anal Pharm Chem. 2022; 9(3): 1149.

Ulcer Index, Analgesics and Anti inflammatory Screening of Some Arylidene Compounds Derived from Phenyl Hydrazine and Aromatic Aldehydes

Salem M¹*, Ayyad R², Sakr H², El-Helby AE², Mansour A³ and Mahmoud K¹

1Medicinal Chemistry Department, Faculty of Pharmacy, Sinai University, Egypt

2Pharmaceutical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Egypt

3Pharmacology department, Faculty of Pharmacy, Al-Azhar University, Egypt

4Pharmaceutical Chemistry department, Faculty of Pharmacy, Egyptian Russian University, Egypt

*Corresponding author: Mo’men Salem, Medicinal Chemistry Department, Faculty of Pharmacy, Sinai University, Northern Sinai, Egypt

Received: August 22, 2022; Accepted: October 14, 2022; Published: October 21, 2022

Abstract

Arylidene derivatives were synthesized from phenyl hydrazine and series of different aldehydes. Arylidene compounds are important classes of N-containing fused heterocycles widely used as key building blocks for pharmaceutical agents due to a wide range of biological activities that include anti-inflammatory and antitumor properties [1]. Arylidene derivatives were furnished by the fusion of benzene ring with different aldehydes via hydrazine moiety in the presence of glacial acetic acid. These derivatives were characterized by TLC, melting points, Infrared Red, Nuclear Magnetic Resonance and Mass Spectroscopy. Finally, these synthetized derivatives were tested for analgesic activity using hot plate test method, anti-inflammatory activity using rat paw oedema and ulcer index test.

Keywords: Arylidene; phenyl hydrazine; Aromatic aldehydes; Benzylidenes; Analgesic activity; Anti-inflammatory activity; Hot plate test; Rat paw oedema; Ulcer index

Introduction

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are a significant class of pharmacological agents with broad therapeutic applications in the treatment of fever, inflammation, and pain [2]. Their application in the treatment of chronic inflammatory diseases, like Rheumatoid Arthritis (RA) and Osteoarthritis (OA) for long period of time was found to have negative side effects which limits their clinical utility [2]. The reported mechanism of NSAID-associated GI adverse effects is the suppression of prostaglandin biosynthesis from arachidonic acid by nonselective inhibition of the two isoforms of Cyclooxygenase (COX) enzyme (COX-1 and COX-2) (2). The tricyclic selective COX-2 inhibitors (coxibs) like celecoxib, rofecoxib, and valdecoxib showed remarkable gastrointestinal safety profile with the same antiinflammatory efficacy as classical NSAIDs. However, concerns about the cardiovascular safety of coxibs have been raised after withdrawal of rofecoxib and valdecoxib from the market [3,4]. It was suggested that the presence of certain moieties within the chemical structure of coxibs are responsible for the increased cardiovascular risk [5]. Therefore, continuous research on the development of novel antiinflammatory agents with increased COX-2 selectivity while moving away from the classic coxib structures could provide agents with improved cardiovascular and GI safety profiles [5]. It was reported that the usage of arylidene moeities considered as a corner stone in the synthesis of many biologically active moleculess especially as antiinflammatory and anticancerous agents [6,7]. In this work, organic compounds using phenyl hydrazine and series of aromatic aldehydes are synthetized and tested for their anti-inflammatory, analgesic and ulcerogenic activity. We targeted the synthesis of compounds formed of benzene ring attached by hydrazine moiety which is two nitrogen atoms but not fused in the ring as Phthalazines, Quinazolines, Quinoxalines or Benzimidazoles [8-20]. These new compounds having two nitrogen atoms in side chain as a bridge between benzene ring and aromatic aldehydes.

Materials

Reagents

All solvents and reagents were obtained from commercial sources and were used without further purification except Glacial Acetic acid and Petroleum Ether (PE). Phenyl Hydrazine was purchased from Sigma Aldrich (Cairo, Egypt). Series of Aromatic Aldehydes were acquired from Sigma Aldrich (Cairo, Egypt). Absolute Ethanol, Ehanol 95%, Glacial Acetic Acid, Ethyl Acetate, Petroleum Ether and Chloroform were purchased from Piochem (Cairo, Egypt). Distilled water was used for the experiments.

Instruments

Progress of chemical reactions was observed using TLC (Merck, silica gel plates 60 F254) and visualized using a UV–Vis spectrometer at 254 nm. Melting points were determined by Mel-Temp apparatus. NMR spectra were performed in Chloroform (7.26 ppm), with trimethyl silane as an internal standard, using Bruker Avance 500 spectrometer at ambient temperature, at drug discovery unit, Faculty of Pharmacy, Ain Shams University (ASU, Cairo, Egypt). All chemical shifts were expressed in parts per million (d), and coupling constants (J) in Hz. FTIR spectra were recorded using KBr pellets on a model 883 double beam infrared spectrophotometer Bruker in 200– 4000 cm-1, at drug discovery unit, Faculty of Pharmacy, Ain Shams University (ASU,Cairo, Egypt). MS spectra were recorded using a Bruker Esquire 2000 by APC or ES ionization, at drug discovery unit, Faculty of Pharmacy, Ain Shams University (ASU, Cairo, Egypt).

Hot Plate Test for Analgesic Activity

Eighty-four male Swiss albino mice (22 ± 2 gm), 6-8 weeks of age were used in this study. The animals were obtained from the breeding colony maintained at the animal house of the El-Nile Pharmaceutical and Chemical Industries Company, Cairo, Egypt. Animals were kept in a controlled environment (25 ± 2°C, 50 ± 5 % humidity) under a 12-hour light/dark cycle and had free access to a standard pellet chow and tap water throughout the study. All experiments were conducted at Al-Azhar University, Faculty of Pharmacy, Cairo, Egypt. Experiments were conducted according to the recommendations of the ethics committee for animal welfare and have been approved by Institutional Animal Care and Utilization. Hot plate test was used to estimate analgesic activity by the method explained by Eddy and Leimbach [21]. Mice were retained on a hot plate having a stable temperature of 55 ± 1°C. The time taken for either paw licking or jumping was recorded. Each mouse was individually placed on the hot plate in order to find the animal’s reaction to electrical heatinduced pain (licking of the fore paws and eventually jumping). The latency until mice showed first signs of discomfort (hind paw lifting, hind paw licking, or jumping) were recorded, before (baseline), and response was determined after 60 min the administration of normal saline, indomethacin (10 mg/kg), diclofenac sodium (7 mg/ kg) (Figure 1) and the tested compounds (1-11) (Figure 2) (10mg/ kg). Data were analyzed using statistical software Graph Pad Prism version 5. One-way analysis of variance (ANOVA) test was used to ascertain the significance of variations between the times of licking in hot plate test. All data were considered significant at p< 0.05 [22].