Date of Award
Doctor of Philosophy (PhD)
Dr. Ibrahim M.Abdo
Dr. Haythem A. Saadeh
Dr. Ahmed H. Al-Marzouqi
Increasing incidence of anticancer and antimicrobial resistance are the most common concerns in the medical field. Cancer is a serious disease that can affect almost every tissue lineage in the human body and poses great challenges to medicinal science. In addition, many antibiotics have a tendency to becoming resistant and are prone to severe adverse effects after long term use. Hence, there is an urgent need to discover and develop novel antitumor drug molecules which could effectively inhibit proliferative pathways with fewer side effects. Also, increasing demand to synthesize novel antimicrobial agents that are active against resistant strains.
This research aimed to design, synthesis, physical studies and biochemical evaluated of some novel pyrazolones and their corresponding ribonucleoside, deoxyribonucleoside and benzoyl analogues for their in vitro antimicrobial and anticancer activities.
Antimicrobial properties of the title compounds were investigated against Gram positive and Gram negative bacterial as well as fungal strains. Anticancer activity was performed against HL60 cell lines. Antimicrobial activity results revealed that the synthesized azo compound 113c, and the synthesized nucleosides compounds 116a and 118c were found to be the most effective agents with better MIC values, compared to some existing antimicrobial drugs, such as Ceftriaxone and Amphotericin B. On the other hand, the results of anticancer study indicated that the synthesized nucleosides 117a, 122a,b and 123 were found to be most potent anticancer agent against the cancerous HL60 cell line while the synthesized nucleosides 117e,f, 122a and the benzoylated compounds 124c,d,f, and 124g showed good affect against the A-549 cell line. Also, pyrazolones derivatives are more sensitive against the lung cancer.
Binding affinity and selectivity of the synthesized compounds towards ct-DNA were studied at different conditions of pH and solvents; the results showed that compound 118c interact and stabilize the ct-DNA which can be anti-cancer agent.
Therefore, these compounds, open new avenues for the development of antibacterial and anti-cancer therapeutic agents for the treatment of infectious and cancer diseases. Also, these results give an insight into the structure-activity relationships, which are tremendously important for the design of further new antimicrobial and anticancer agents.
Aboukhousa, Heba Ahmed Ghanim, "Regioselective Synthesis of Biologically Active Pyrazolone Nucleosides and their Benzoyl Analogues" (2017). Philosophy Dissertations. 5.