Doctoral thesis will be focused on the projecting, synthesis and microbiological evaluation of novel potential antimycobacterial active compounds derived from pyrazinecarboxylic acid. To design new drugs with potential anti-mycobacterial activity by structural modification of the known and used anti-tuberculosis drug “pyrazinamide”. This PhD project will focus on nitrogen containing heterocyclic derivatives of 6-fluoropyrazinamide, including five membered rings containing two nitrogen atoms (histidine), six membered rings contacting two nitrogen atoms (salicylic moiety), nitrogen and oxygen contacting heterocycles attached to a benzene ring (1,4-benzoxazine), among others. To test all compounds for in vivo activity against M. tuberculosis and/or M. avium, M. kansasii, M. smegmatis, along anti-fungal and anti-bacterial activity against selected strains. Equipment and Methods Expected to Be Needed: Drug design and docking; Microwave assisted synthesizer; Preparative column chromatograph; Physic-chemical properties calculation; In vitro biologic screening; Structure activity relationship (SAR). The study program will also include: Passing certain exams (Organic Chemistry, Microbiology, Computer-Aided Drug Design, Medicinal Chemistry, defense of the Ph.D. thesis); Taking part in pre-graduate practical training in Medicinal Chemistry; Participating in Grant Agency of Charles University and other competitions for research funding; One semester research stay (ERASMUS/SOCRATES, bilateral collaboration focused on developing antibiotics) in another European state; Participating in conferences (posters, lectures) in Czech Republic and in Europe; Publishing achieved results in scientific journals.
- zadáno a potvrzeno stud. odd.