Design and Synthesis of New Compounds Derived from Phenyl Hydrazine and Different Aldehydes as Anticancer Agents

Research Article

Austin J Anal Pharm Chem. 2022; 9(1): 1141.

Design and Synthesis of New Compounds Derived from Phenyl Hydrazine and Different Aldehydes as Anticancer Agents

Salem M¹*, Ayyad R², Sakr H² and Gaafer A³

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

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

³Medical Services Sector, Interior Ministry, Egypt

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

Received: February 21, 2022; Accepted: March 17, 2022; Published: March 24, 2022

Abstract

In this work we synthesized new derivatives from Phenyl Hydrazine and series of different Aldehydes (derivatives of benzylidenes). The synthesized compounds contain different aromatic Aldehydes which attached by Benzene ring via Hydrazine moiety. These derivatives were characterized by TLC, melting points, Infrared Red, Proton Nuclear Magnetic Resonance, Carbon Thirteen Nuclear Magnetic Resonance and Mass Spectroscopy. Finally, these synthesized derivatives were tested for antiproliferative activity against multiple normal and cancerous cell lines, HepG2 (Liver Cancer) and MCF-7 (Breast Cancer) cell lines were used for cytotoxic assay.

Keywords: Phenyl hydrazine; Aromatic aldehydes; Benzylidene synthesis; Cytotoxic assay; Anticancer; HepG2; MCF-7

Introduction

Cancer is a public health menace. The disease is of a great concern to both developed and developing countries due to its high morbidity and mortality. In many countries, it has become second largest killer after cardiovascular disease [1]. In 2012, there were 14 million new cases and 8.2 million deaths [1]. Among men, lung cancer was the most predominant, while among women, it was breast cancer. It was reported that there were 24 million cancer cases annually and 14.6 million annual deaths by the end of 2015 [2]. These troubling figures compel policy makers and the researchers to combat this disease. Cancer is a collection of different life-threatening diseases characterized by uncontrolled growth of cells leading to invasion of surrounding tissue and often spreading to other parts of the body [3]. When it comes to understanding and controlling cancer scientists are now working from a position of strength because a foundation of knowledge about cancer has been built over the past 50 years. There is an urgent need for novel effective drug regimens for the treatment of cancer because the current chemotherapy suffers from a slim therapeutic index, with significant toxicity from effective drug doses or tumor recurrence at low drug doses. The new anticancer chemotherapeutic agents search continues to be an active area of research at many companies and research centers [3,4]. Searching for new anticancer agents having heterocyclic nucleus continues worldwide at various laboratories [5-7]. So these organic compounds synthesized and tested as anticancer drugs. Synthesized compounds have benzene ring attached to five or six membered rings (Benzimidazole) or (Phthalazine, Quinazoline, Quinoxalines). In this work we aimed the synthesis of organic 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. These new compounds have two nitrogen atoms in side chain as a bridge between benzene ring and aromatic aldehydes [8-44].

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-Visspectrometer at 254nm. Melting points were determined by Mel-Temp apparatus. NMR spectra were performed in Chloroform(1) (7.26ppm), 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- 4000cm-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).

Cell culture: HepG2, MCF-7

Cell line was obtained from Nawah Scientific Inc., (Mokatam, Cairo, Egypt). Cells were maintained in DMEM media supplemented with 100mg/mL of streptomycin, 100nits/mL of penicillin and 10% of heat-inactivated fetal bovine serum in humidified, 5% (v/v) CO2 atmosphere at 37°C [45,46].

Cytotoxicity assay: Hep G2, MCF-7

Cell viability was assessed by SRB assay. Aliquots of 100μL cell suspension (5x10^3 cells) were in 96-well plates and incubated in complete media for 24h. Cells were treated with another aliquot of 100μL media containing drugs at various concentrations. After 72h of drug exposure, cells were fixed by replacing media with 150μL of 10% TCA and incubated at 4°C for 1h. The TCA solution was removed, and the cells were washed 5 times with distilled water. Aliquots of 70μL SRB solution (0.4%w/v) were added and incubated in a dark place at room temperature for 10min. Plates were washed 3 times with 1% acetic acid and allowed to air-dry overnight. Then, 150μL of TRIS (10mM) was added to dissolve protein-bound SRB stain; the absorbance was measured at 540nm using a BMG LABTECH®- FLUOstar Omega microplate reader (Ortenberg, Germany) [45,46].

Chemistry and Scheme

Scheme

See Figure 1.