QUANTUM MODELING OF SOME POTENT NON-TOXIC ANTI-TUBERCULOSIS COMPOUNDS

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QUANTUM MODELING OF SOME POTENT NON-TOXIC ANTI-TUBERCULOSIS COMPOUNDS

 

CHAPTER ONE

1.0 INTRODUCTION

1.1 Background to the Study

Despite the fact that tuberculosis (TB) has been recognized for thousands of years and despite the fact that the etiological agent has been identified since earliest days of medical biology, the global burden of TB continues to loom as one of the largest among infectious diseases, with an enormous toll in morbidity and mortality (Leonard and Rachael,2009).This disease which is caused by various strains of mycobacteria, usually Mycobacterium tuberculosis (MTB) isthe leading cause of death from a single infectious agent, after the human immuno deficiency virus (HIV) (WHO, 2013). Currently, one-third of the world harbors the latent form of Mycobacterium tuberculosis, with a lifelong risk of activation and disease development, particularly in people co-infected with HIV (Anil et al., 2011). The World Health Organization (2014) reported 1.5 million deaths from tuberculosis globally in 2013 andout of this number, 360,000 were HIV-positive. Ironically, available therapeutic agents are highly efficacious in TB treatment, withcure exceeding 95% during clinical trials (Frieden, 2003). The natural question is; why then has the control of TB been so problematic?

The answer lies in the indolent clinical nature of the disease, whichneeds prolonged complex therapy and the unusual microbiological properties of the pathogen(Leonard and Rachael, 2009). The actual drug therapy for tuberculosis involves the administration of multiple drugs because it was clear that monotherapy led to the development of resistance (Barry and Blanchard, 2010).The current short-course TB therapy used to treat drug-susceptible MTB consists of months of treatment with four so-called first-line drugs including rifampin (RIF), isoniazid (INH),pyrazinamide (PZA) and ethambutol (EMB), followed by 4- months treatment with RIFand INH (Sunduru et al.,2010). Infection by multidrug resistant tuberculosis (MTR-TB) strains requires treatment with second-line drugs such askanamycin, amikacin, capreomycin,p-aminosalicylate (PAS), fluoroquinolones(levofloxacin, gatifloxacin and moxifloxacin), ethionamide (ETH), and cycloserine wheretreatments often extend for up to long 2 years (Janin, 2007). This Chemotherapy is less effective, longer, expensive and more toxic than the short course therapy (Ma et al., 2010). Third line drugs include rifabutin, macrolides (clarithromicin), linezolid, thiacetazone, thioridazine, arginine, vitamin D are still being developed, have less or unproven efficacy and are very expensive (Lalloo and Ambaram, 2010).

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QUANTUM MODELING OF SOME POTENT NON-TOXIC ANTI-TUBERCULOSIS COMPOUND