The structures of a series of complexes with general formula n[Pd(pza)X]Y·mH2O (n = 1, 2; X = Cl, Br, I, N3, NCS; Y = NO3, I, N3, [Pd(SCN)4]; m = 0, 0.5, 1) have been determined, where pza is the tridentate ligand bis-[2-(3,5-di-methyl-pyrazol-1-yl)eth-yl]amine, C14H23N5. In all complexes, {bis-[2-(3,5-di-methyl-pyrazol-1-yl-κN (2))eth-yl]amine-κN}chlorido-palladium nitrate, [Pd(pza)Cl]NO3, (1)...

PURPOSE Pyrazoloacridine (PZA) is an investigational nucleic acid binding agent that inhibits the activity of topoisomerases I and II through a mechanism distinct from other topoisomerase poisons. PZA shows schedule-independent cytotoxicity against tumor cells, whereas host toxicity is greater with shorter infusions. We assessed the clinical toxicities and pharmacologic effects of PZA given as ...

Pyrazoloacridine (NSC 366140, PD115934, PZA) is a new class of acridine anticancer agents under investigation in Phase II clinical trials in patients with advanced cancers. Although poor responses in patients to the treatment with PZA alone have been observed, this class of agents remains of interest because of its distinct mechanism of action from other topoisomerase poisons. Therefore, the co...

7. Timetable of Work: Document the study progress according to the proposed timetable. This study involved eligible culture isolates of M. tuberculosis consecutively received by Queen Mary Hospital Microbiology Laboratory serving patients in Queen Mary Hospital and Graham Hospital with M. tuberculosis isolated since 1 Jun 2013. During the first month of study (March 2015), ordering of necessary...

BACKGROUND Pyrazinamide is a paradoxical frontline tuberculosis drug characterized by high in vivo sterilizing activity but poor in vitro activity. This separation in pyrazinamide activity reflects differences between the in vivo tissue environment and in vitro culture conditions. The well-known acid pH requirement for pyrazinamide activity was discovered previously based on such reasoning but ...

Despite the important role of pyrazinamide in tuberculosis treatment, little is known about the mechanism of pyrazinamide-induced hepatotoxicity. We inhibited xanthine oxidase in HepG2 cells by using a nontoxic concentration of allopurinol, a well-known xanthine-oxidase inhibitor. This increased in vitro pyrazinamide toxicity in HepG2 cells, which suggests that the hydroxy metabolites of pyrazi...

BACKGROUND In South Africa, drug resistant tuberculosis is a major public health crisis in the face of the colossal HIV pandemic. METHODS In an attempt to understand the distribution of drug resistance in our setting, we analysed the rpoB, katG, inhA, pncA and embB genes associated with resistance to key drugs used in the treatment of tuberculosis in clinical isolates of Mycobacterium tubercu...

BACKGROUND Mutations in pncA and gyrA genes cause pyrazinamide (PZA) and fluroquinolone resistance in Mycobacterium tuberculosis (MTB). In the present study, structures of pyrazinamidase (PZase) and DNA gyrase proteins were studied in resistant and susceptible clinical isolates of MTB. MATERIALS AND METHODS Sixty clinical isolates of MTB were used in this study. Polymerase chain reaction (PCR...

To determine the prevalence and molecular characteristics of drug-resistant tuberculosis in Hunan province, drug susceptibility testing and spoligotyping methods were performed among 171 M. tuberculosis isolates. In addition, the mutated characteristics of 12 loci, including katG, inhA, rpoB, rpsL, nucleotides 388 to 1084 of the rrs gene [rrs(388-1084)], embB, pncA, tlyA, eis, nucleotides 1158 ...

Mycobacterium tuberculosis pyrazinamidase (PZAse) is a key enzyme to activate the pro-drug pyrazinamide (PZA). PZAse is a metalloenzyme that coordinates in vitro different divalent metal cofactors in the metal coordination site (MCS). Several metals including Co(2+), Mn(2+), and Zn(2+) are able to reactivate the metal-depleted PZAse in vitro. We use quantum mechanical calculations to investigat...