OBJECTIVE: A series of new pyrazolines containing novel 2,5-dichloro-3-acetylthiophene chalcone moiety (PZT1-PZT20) have been synthesized, characterized by 1HNMR and 13CNMR and evaluated for them in vitro antitubercular activity against M. tuberculosis H37Rv strain and in vitro anticancer activity against DU-145 prostate cancer cell lines and all compounds were also screened for molecular docking studies against specific targeted protein domains.
METHODS: All compounds were screened for potential activity against Mycobacterium tuberculosis H37Rv (MTB) strain and anticancer activity against DU-149 prostate cancer cell lines using MTT cytotoxicity assay.
RESULTS: Among the series, compound PZT5 with 2", 4"-dichlorophenyl group at 5-position on the pyrazoline ring exhibited the most potent antitubercular activity (MIC=1.60 µg/mL) and compounds PZT2, PZT9, PZT11, PZT15, and PZT20 showed similar antitubercular activity against standard pyrazinamide (MIC=3.12 µg/mL) by broth dilution assay. PZT15 and PZT17 with 4"- pyridinyl and 2"-pyrrolyl groups on pyrazoline ring were found to exhibit better anticancer activity against DU-149 prostate cancer cell lines with IC50 values of 2.0±0.2 µg/mL and 6.0±0.3 µg/mL respectively by MTT assay. The preliminary structure-activity relationship has been summarized. The molecular docking studies with crystalline structures of enoyl acyl carrier protein reductase InhA interaction with target protein (2NSD; PDB and 3FNG; PDB) of Mycobacterium tuberculosis H37Rv (MTB) strain have also exhibited good ligand interaction and binding affinity. Ligand interaction and binding affinity were estimated using crystal structures of both types of enoyl acyl carrier protein reductase InhA (3FNG.pdb) and found to be much higher (-16.70 to - 19.20 kcal/mol) compared with pyrazinamide (-10.70 kcal/mol) as a standard target molecule. Whereas the binding affinities of six active compounds with crystal structure of other type of enoyl acyl carrier protein reductase InhA (2NSD.pdb) were much similar and higher (-9.30 to - 11.20 kcal/mole) than pyrazinamide (-11.10 kcal/mole).
CONCLUSION: These new pyrazolines would be promising potent inhibitors of drug sensitive and drug resistant Mycobacterium tuberculosis strain and potential anticancer agents against prostate cancer and other prototypes of cancers.
METHODS: We conducted a retrospective review of TB cases notified in Sabah, Malaysia, between 2012 and 2018. Using data from the state's 'myTB' notification database, we calculated the case notification rate and described trends in the epidemiology, diagnostic practices and treatment outcomes of TB in Sabah within this period. The Chi-squared test was used for determining the difference between two proportions.
RESULTS: Between 2012 and 2018 there were 33 193 cases of TB reported in Sabah (128 cases per 100 000 population). We identified several geographic hotspots, including districts with > 200 cases per 100 000 population per year. TB rates increased with age and were highest in older males. Children
OBJECTIVE: To obtain population-based data on Mycobacterium tuberculosis drug resistance in Pakistan.
METHODS: To obtain drug resistance data, we conducted a population-based study of TB cases in all provinces of Pakistan. We performed culture and drug susceptibility testing on M. tuberculosis isolates from patients with a prior history of anti-tuberculosis treatment (retreatment cases) from all over the country.
RESULTS: Of 544 isolates from previously treated cases, 289 (53.1%) were susceptible to all first-line drugs, 255 (46.9%) were resistant to at least one anti-tuberculosis drug and 132 (24.3%) were MDR-TB. Among MDR-TB isolates, 47.0% were ofloxacin (OFX) resistant. Extensively drug-resistant TB was found in two (0.4%) isolates.
CONCLUSION: Prevalence of drug resistance in retreatment isolates was high. The alarmingly high prevalence of OFX resistance among MDR-TB isolates may threaten the success of efforts to control and treat MDR-TB.
METHODS: This retrospective cohort study involved laboratory-confirmed drug-resistant TB patients from January 2009 to June 2013. Multiple logistic regression was used to model the outcome, which was subsequently defined according to the recent definition by the WHO. Data were analysed using IBM SPSS Statistics for Windows version 22.0.
RESULTS: Among the 403 patients who were analysed, 66.7% of them were found to have achieved successful outcomes (cured or completed treatment) while the remaining 33.3% had unsuccessful treatment outcomes (defaulted, treatment failure or died). Multivariable analysis showed that the type of resistance [polyresistant (aOR = 3.00, 95% CI 1.14-7.91), multidrug resistant (MDR) (aOR = 5.37, 95% CI 2.65-10.88)], ethnicity [Malay (aOR = 2.86, 95% CI 1.44-5.71), Indian (aOR = 3.04, 95% CI 1.20-7.70)], and treatment non-compliance (aOR = 26.93, 95% CI 14.47-50.10) were the independent risk factors for unsuccessful treatment outcomes among this group of patients. Notably, the odds of unsuccessful treatment outcome was also amplified among Malay MDR-TB patients in this study (aOR = 13.44, 95% CI 1.99-90.58).
CONCLUSION: In order to achieve better treatment outcomes for TB, effective behavioural intervention and thorough investigation on ethnic disparities in TB treatment are needed to promote good compliance.