Combination formulation development for a new antiasthmatic bronchodilatory agent

Abstract

Asthma is an inflammatory disease of the airways that affects 5 10% of the general population. Epidemiological studies indicate that there is a global increase in the incidence, morbidity, and mortality caused by asthma despite an expanding repertoire of medications available for the treatment of this disease. The chronic inflammation is associated with airway obstruction and mucus production that leads to increased airway hyper-responsiveness resulting to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. Oxidative stress describes the damage that occurs when ROS overwhelm the antioxidant defences of the host. In asthma, this oxidative stress can have many detrimental effects on airway function, including airway smooth muscle contraction. Natural products are diverse sources of important chemical constituents, most of them being heterocyclic. These molecules have diverse pharmacological actions. One of such heterocyclic compounds is vasicine. The alkaloid is derived from the highly reputed plant Adhatoda vasica Nees, family Acanthaceae, its leaves have been used in Indian system medicine for more than 2000 years. Vasicine was found to have bronchodilatory activity. It was reported to cause relaxation of tracheal muscle at low concentrations and contraction at high concentrations. It also exhibited protection against histamine induced bronchospasm. NNOHO newlineFigure: Structure of Vasicinone For the possibility that one of vasicine s congeners could possess potent bronchodilator activity, various vasicine analogues were prepared and proved fruitful.