Design and synthesis of novel nitrothiazolacetamide conjugated to different thioquinazolinone derivatives as anti-urease agents.

The present article describes the design, synthesis, in vitro urease inhibition, and in silico molecular docking studies of a novel series of nitrothiazolacetamide conjugated to different thioquinazolinones. Fourteen nitrothiazolacetamide bearing thioquinazolinones derivatives (8a-n) were synthesized through the reaction of isatoic anhydride with different amine, followed by reaction with carbon disulfide and KOH in ethanol. The intermediates were then converted into final products by treating them with 2-chloro-N-(5-nitrothiazol-2-yl)acetamide in DMF. All derivatives were then characterized through different spectroscopic techniques (1H, 13C-NMR, MS, and FTIR). In vitro screening of these molecules against urease demonstrated the potent urease inhibitory potential of derivatives with IC50 values ranging between 2.22 ± 0.09 and 8.43 ± 0.61 µM when compared with the standard thiourea (IC50 = 22.50 ± 0.44 µM). Compound 8h as the most potent derivative exhibited an uncompetitive inhibition pattern against urease in the kinetic study. The high anti-ureolytic activity of 8h was confirmed against two urease-positive microorganisms. According to molecular docking study, 8h exhibited several hydrophobic interactions with Lys10, Leu11, Met44, Ala47, Ala85, Phe87, and Pro88 residues plus two hydrogen bound interactions with Thr86. According to the in silico assessment, the ADME-Toxicity and drug-likeness profile of synthesized compounds were in the acceptable range.

Minimally invasive radioguided parathyroid surgery using low-dose Tc-99m-MIBI - comparison with standard high dose.

INTRODUCTION: Surgery remains the most effective treatment for primary hyperparathyroidism (PHPT). Minimally invasive radioguided parathyroidectomy (MIRP) is a common technique for detecting and excising abnormal parathyroid glands. The aim of this study was to compare injections of low-dose and high-dose (99m) Tc methoxy isobutyl isonitrile (MIBI) for intraoperative localisation of parathyroid adenomas by means of a gamma probe in patients with primary hyperparathyroidism (PHPT). MATERIAL AND METHODS: Thirty patients with PHPT and a preoperative diagnosis of parathyroid adenoma were enrolled between 2010 and 2012. They were considered as Group B and underwent MIRP using 5 mCi Tc-99m MIBI, and their perioperative data were compared with twenty patients treated with conventional 20 mCi Tc-99m MIBI previously (Group A). RESULTS: Group A was made up of 20 patients (mean age, 41.55 years; 14 women and 6 men), and group B included 30 patients (mean age, 40.43 years; 19 women and 11 men). The mean serum parathyroid hormone (PTH) and calcium values were recorded pre- and postoperatively. The mean follow-up period for the patients in the two groups was 18.4 and 16.5 months, respectively. Pre-operative evaluation demonstrated that the groups were statistically similar. Intraoperative data and success rate of surgery showed no difference between the two groups. No significant complication was detected after surgeries and no recurrence happened in either of the two groups during the follow-up period. CONCLUSIONS: A new protocol of MIRP using low doses of Tc-99m-MIBI resulted in an excellent success rate. Comparing results of the study, we conclude that low-dose Tc-99m-MIBI may be preferred for identification of parathyroid adenomas intraoperatively by means of a gamma probe in PHPT patients because it appears to be as effective as high-dose Tc-99m-MIBI.