We report in this article an extensive structure-activity relationships (SAR) study with 58 thiophen-2-yl-1,2,4-oxadiazoles as inhibitors of EthR, a transcriptional regulator controling ethionamide bioactivation in Mycobacterium tuberculosis. We explored the replacement of two key fragments of the starting lead BDM31343. We investigated the potency of all analogues to boost subactive doses of ethionamide on a phenotypic assay involving M. tuberculosis infected macrophages and then ascertained the mode of action of the most active compounds using a functional target-based surface plasmon resonance assay. This process revealed that introduction of 4,4,4-trifluorobutyryl chain instead of cyanoacetyl group was crucial for intracellular activity. Replacement of 1,4-piperidyl by (R)-1,3-pyrrolidyl scaffold did not enhance activity but led to improved pharmacokinetic properties. Furthermore, the crystal structures of ligand-EthR complexes were consistent with the observed SAR. In conclusion, we identified EthR inhibitors that boost antibacterial activity of ethionamide with nanomolar potency while improving solubility and metabolic stability.

Objectives: The aim of this study was to determine the prevalence of root dilaceration in a Turkish dental patient population with respect to sexes and dental localization in relation between sex and this anomaly. Study Design: A retrospective study was performed using periapical radiography of 2,124 patients ranging in age from 15 to 65. All data (age, sex and systemic disease or syndrome) was obtained from the files. These patients were analyzed for root dilaceration. Descriptive characteristics of sexes, jaws, and dental localization were recorded. The Pearson chi-squared test was used. Results: Of 2,251 patients, 214 (9.5%) had root dilaceration. Root dilacerations were determined in 276 (4.3%) of 6386 teeth belong to 2251 patients. Anomalies were found in 9.8% of males compared with 9.3% of females. However, this difference was not statistically significant (p>0.05). Root dilacerations were similarly distributed between maxilla and mandible. The most frequently root dilacerated teeth were found to be mandibular third molars (12.8%), followed by maxillary third molars (7.4%), maxillary first molars (6.7%). Root dilaceration was not detected in maxillary central incisors, mandibular central incisors and mandibular lateral incisors. Conclusion: According to our results, root dilaceration is an uncommon developmental anomaly which mostly occurs in the posterior teeth that is not also possible to have trauma. The radiographic diagnosis of this anomaly is important before surgery and orthodontics treatment, but firstly endodontic treatment.

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