Drug Discovery

Researchers at the Department of Pharmaceutical Sciences consider the subtheme of drug discovery as the main area of research in phytochemistry and medicinal chemistry specialties. Their research activities focus on the discovery of drugs from natural or synthetic origin that could have biological and or pharmacological effects.

Within the framework of this concept, our phytochemistry research team continue working on endemic Lebanese species, and the work extended to include other colleagues from different disciplines. Our recent article:Cytotoxic Activity of Alkaloids from Lebanese Papaver rhoeas, demonstrated the chemical investigation of Lebanese Papaver rhoeaswhere five alkaloids were identified. These alkaloids showed promising activity with cell line specificity, selectivity, and minimal toxicity to normal cells. Moreover, analgesic and anti-inflammatory activities of these alkaloids were evaluated in vivo, and compared to standard drugs.

Another recent research article: Anti-inflammatory and Antioxidant Activities of Salvia fruticosa: An HPLC Determination of Phenolic Contents, confirmed the antioxidant and anti-inflammatory activities of the common Lebanese plant S. fruticose. The antioxidant activity was correlated to the total phenolic content of the plant that were determined and its chemical constituents were also identified using HPLC.

Other studies also focus on antidiabetic effects and neuroprotectives activities of medicinal plants. A good example is the article entitled: Acute and subchronic in-vivo effects of Ferula hermonis and Sambucus nigra and their potential active isolates in a diabetic mouse model of neuropathic pain. This article described the activities of F. hermonis and S. nigra aqueous extracts in a diabetic mouse model of neuropathic pain. The extracts showed remarkable hypoglycemic and antinociceptive activities compared to glibenclamide and tramadol, as positive controls.

The Medicinal Chemistry team is currently working on designing and synthesis of heterocyclic compounds with potential biological activities. As an extension to our previous work, and owing to emerging need to discover new antitumor drugs, our team is interested in design and synthesis of novel pyrimidinone derivatives for their anticancer activities. This work led to the publication entitled: Synthesis of novel 1, 5-diphenyl-6-substituted 1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones induced apoptosis in RKO colon cancer cells. Novel pyrimidinone derivatives were synthesized and screened. Some compounds inhibited proliferation and induced apoptosis of colon cancer cells. Cell cycle inhibition phase and probable antiproliferative mechanisms of action were studied. Collectively, our findings could establish a molecular basis for development of new anti-cancer agents, which is directly enriching the field of drug discovery. In agreement with our research goals, a topic was selected for a Master student within the drug discovery subtheme, entitled: Design and synthesis of heterocyclic compounds of biological interest. This study aims to design potential new generations of anticancer and antimicrobial candidates.

Most studies done in Pharmacology and Therapeutics Department are pertinent with discovering the molecular mechanisms of drugs used in the management of the most commonly encountered organ disorders and diseases in order to optimize pharmacotherapy spatially for patients with chronic disease. In this context, the elucidation and the characterization of the molecular mechanisms underlying the beneficial and/or detrimental effects of such drugs are preclinical investigated using pharmacologiocal and biochemical techniques.

A recent research was carried out to explore the harmful cardiovascular effects associated with the use of cyclosporine, an immunosuppressant used worldwide for prevention of rejection of transplanted organs and for treatment of psoriasis. It was found that, renin-angiotensin system interplays with other vasopressor pathways, namely endothelin and thromboxane A2, in mediating the cyclosporine hypertensive and baroreflex impairment actions and that the facilitation of baroreflex control and inhibition of vascular responsiveness to angiotensin II and thromboxane contribute to the blood pressure lowering effect of renin-angiotensin system inhibitors in cyclosporine-treated rats.

Another research team investigated the in-vivo and in-vitro hemodynamic and cardiovascular effects of gabapentin in experimental rats. Gabaptin was first introduced as an antiepileptic drug and later on, it was indicated to treat several chronic pain conditions. Common adverse effects of gabapentin are mainly neuropsychiatric. However, the more serious ones were related to cardiovascular events as arrhythmia and others associated with heart failure.

Our futuristic vision is to direct our research activities towards more integrated domains in order to find out natural sources of drugs with diverse pharmacological effects. In addition, the ongoing and future researches are running aiming at enriching the scientific society with new chemical entities potentially active as chemotherapeutic and or pharmacodynamic agents. Moreover, our pharmacological studies will focus on providing the opportunity of better understanding of disease pathogenesis for the development of more effective drugs to overcome the encountered therapeutic challenges.