Akademik Veri Yönetim Sistemi
Asian Federation of Medicinal Chemistry (AFMC) 12th International Symposium, İstanbul, Türkiye, 8 - 11 Eylül 2019, ss.108-109
Infectious diseases continue to be a threating problem for human health worldwide owing to expanding levels of resistance to antibacterial agents. Varied mechanisms underlie the resistance to antibiotic treatment. Not only mutations that decrease the binding affinity of a drug to its target, but also increased expression of efflux transports cause antibacterial resistance. Fluoroquinolones (FQs) are well-known antibacterial drugs. While FQs have broad spectrum activity covering Gram (+) and Gram (-) strains, they are mostly prescribed against respiratory tract infections, urinary tract infections, gastrointestinal infections and sexually transmitted diseases. Besides, tuberculosis (TB) therapy is the relatively new indication of FQs approved by World Health Organization. TB represents to be one of the deadliest infections that affect 10 million people annually [1,2]. Drug resistance is the major concern regarding with antibacterial chemotherapy. As this point, remarkable urgency to develop new antibacterial and anti-tuberculosis agents has emerged in today’s world. Modifying already known FQ derivatives is a widely accepted and commonly used approach in the area of antibacterial drug discovery. From this point of view, several modified FQ derivatives were designed, synthesized and evaluated for their antibacterial and antimycobacterial activity. Studies were first started with the introduction of azole heterocycle to norfloxacin and ciprofloxacin and evolved to develop novel moxifloxacin derivatives. Compounds showed promising antibacterial and anti-tuberculosis activity compared to tested standard FQ compounds [3,4]. To put more molecular insight into the activity of these compounds,
molecular docking studies were performed. Since FQs act by inhibiting DNA gyrase enzyme of bacteria, compounds were screened in silico against DNA gyrase enzymes of Mycobacterium tuberculosis and Staphylococcus aureus. It is noteworthy to state that the X-ray structure of M. tuberculosis DNA gyrase co-crystallized with DNA and several ligands (moxifloxacin, gatifloxacin, levofloxacin, ciprofloxacin) has been lately published [5]. This breakthrough development has opened new ways to the discovery of new antituberculosis agents which can specifically inhibit M. tuberculosis DNA gyrase. In conclusion, our efforts to develop new antibacterial and antimycobacterial agents will be summarised here.