Synthesis, Antimicrobial Activities of New Sulfonamidobenzoxazoles and Molecular Docking Studies on Escherichia coli TEM-1 β-Lactamase

β-Lactam antibiotics are frequently used for treatment of multi-drug resistant microbial infections and the most common mechanism of resistance against these antibiotics is bacterial β-lactamase production. Herein, we reported the design, synthesis and in vitro antimicrobial activities of some new 2-substituted-5-(2,4-dinitrophenylsulfonamido)benzoxazole derivatives. Compounds TN1, TN2, and TN3 were found to be significantly active against E. coli isolate which contains extended spectrum β-lactamase enzyme at the MIC value of 8 µg mL–1 and that is 4-fold higher than the reference drug ampicillin. We performed molecular docking studies into active site of Escherichia coli TEM-1 β-lactamase enzyme in order to predict the protein-ligand interactions. According to the docking results, compounds TN1, TN2, and TN3 showed strong interactions between the important active site residues which are responsible for the catalytic mechanism of TEM-1 β-lactamase enzyme and a good correlation is found with the experimental data. This work is licensed under a Creative Commons Attribution 4.0 International License

Synthesis and In vitro Antimicrobial Activity of Novel 2-(4-(Substituted-carboxamido)benzyl / phenyl)benzothiazoles

A new series of 2-[4-(4-substitutedbenzamido / phenylacetamido / phenylpropionamido) benzyl / phenyl]benzothiazole derivatives (6a−6w) were synthesized and evaluated for antibacterial and antifungal activities against Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli with their drug-resistant isolates and a yeast Candida albicans. Microbiological results indicated that the compounds possessed a broad spectrum of activity against the tested microorganisms at MIC values between 200 and 6.25 μg/ml. Compounds 6e and 6j exhibited the greatest activity with MIC values of 6.25 μg/ml against Pseudomonas aeruginosa, and Staphylococcus aureus isolate, respectively.(doi: 10.5562/cca2064

Digital Health Technologies to Improve Medication Adherence and Treatment Outcomes in Patients With Tuberculosis:Systematic Review of Randomized Controlled Trials

BACKGROUND: Nonadherence to medication in tuberculosis (TB) hampers optimal treatment outcomes. Digital health technology (DHT) seems to be a promising approach to managing problems of nonadherence to medication and improving treatment outcomes. OBJECTIVE: This paper systematically reviews the effect of DHT in improving medication adherence and treatment outcomes in patients with TB. METHODS: A literature search in PubMed and Cochrane databases was conducted. Randomized controlled trials (RCTs) that analyzed the effect of DHT interventions on medication adherence outcomes (treatment completion, treatment adherence, missed doses, and noncompleted rate) and treatment outcomes (cure rate and smear conversion) were included. Adult patients with either active or latent TB infection were included. The Jadad score was used for evaluating the study quality. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline was followed to report study findings. RESULTS: In all, 16 RCTs were selected from 552 studies found, and 6 types of DHT interventions for TB were identified: 3 RCTs examined video directly observed therapy (VDOT), 1 examined video-observed therapy (VOT), 1 examined an ingestible sensor, 1 examined phone call reminders, 2 examined medication monitor boxes, and 8 examined SMS text message reminders. The outcomes used were treatment adherence, including treatment completion, treatment adherence, missed dose, and noncompleted rate, as well as clinical outcomes, including cure rate and smear conversion. In treatment completion, 4 RCTs (VDOT, VOT, ingestible sensor, SMS reminder) found significant effects, with odds ratios and relative risks (RRs) ranging from 1.10 to 7.69. Treatment adherence was increased in 1 study by SMS reminders (RR 1.05; 95% CI 1.04-1.06), and missed dose was reduced in 1 study by a medication monitor box (mean ratio 0.58; 95% CI 0.42-0.79). In contrast, 3 RCTs of VDOT and 3 RCTs of SMS reminders did not find significant effects for treatment completion. Moreover, no improvement was found in treatment adherence in 1 RCT of VDOT, missed dose in 1 RCT of SMS reminder, and noncompleted rate in 1 RCT of a monitor box, and 2 RCTs of SMS reminders. For clinical outcomes such as cure rate, 2 RCTs reported that phone calls (RR 1.30; 95% CI 1.07-1.59) and SMS reminders (OR 2.47; 95% CI 1.13-5.43) significantly affected cure rates. However, 3 RCTs found that SMS reminders did not have a significant impact on cure rate or smear conversion. CONCLUSIONS: It was found that DHT interventions can be a promising approach. However, the interventions exhibited variable effects regarding effect direction and the extent of improving TB medication adherence and clinical outcomes. Developing DHT interventions with personalized feedback is required to have a consistent and beneficial effect on medication adherence and outcomes among patients with TB

Benzothiazole derivatives as human DNA topoisomerase IIα inhibitors

Abstract Benzothiazole derivatives resembling the structure of DNA purine bases were tested to determine their topoisomerase inhibition activities. Based on DNA topoisomerase I and II relaxation assay results, all 12 derivatives acted as human topoisomerase IIa inhibitors, whereas only two compounds inhibited Calf thymus topoisomerase I. 3-amino-2-(2-bromobenzyl)-1,3-benzothiazol-3-ium 4-methylbenzensulfonate (BM3) was observed to be the most effective human topoisomerase IIa inhibitor with the lowest IC 50 value of 39 nM. The mechanistic studies suggested that BM3 was neither a DNA intercalator nor a topoisomerase poison, it was only a DNA minor groovebinding agent. BM3 initially bound to the DNA topoisomerase IIa enzyme, then to DNA. As a result, the tested benzothiazole derivatives were obtained as strong topoisomerase IIa inhibitors. The benzothiazole tosylated salt form BM3 was found as the most effective topoisomerase IIa inhibitor. BM3's mechanisms of action might be its direct interaction with the enzyme. BM3's minor groove-binding property might also contribute to this action. Hence, BM3 could be a good candidate as a new anticancer agent

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

The 12(th) AFMC International Medicinal Chemistry Symposium (AIMECS 2019) in Istanbul, Turkey

AFMC-AIMECS meetings are internationally organized biannually by the Asian Federation for Medicinal Chemistry (AFMC) and are focused on recent studies in drug discovery and development both in academia and industry. Member organizations of the AFMC are the Pharmaceutical Society of Japan, the Chinese Pharmaceutical Association, the Royal Australian Chemical Institute, the Pharmaceutical Society of Korea, the Korean Chemical Society, the Chemical Society Located in Taipei, the Indonesian Society of Medicinal Chemistry, the Medicinal Chemistry Section of the Israel Chemical Society, and the Computer-Aided Drug Design \& Development Society in Turkey. Each time, the symposium is organized within these member countries. The AIMECS 2019 symposium was held in Turkey this year, as Prof. Dr. Esin Aki-Yalcin is the current president of the AFMC (2018-2020); the next AIMECS meeting will be organized in 2021 in Tokyo, Japan. In this report, we discuss key topics at the 12(th) AFMC International Medicinal Chemistry Symposium - New Avenues for Design and Development of Translational Medicine (AIMECS 2019) held in Istanbul, September 8-11, 2019

Development and Evaluation of a Training Program for Organ Procurement Coordinators Using Standardized Patient Methodology

WOS: 000442098600019PubMed ID: 26643104Objectives: The low rate of consent by next of kin of donor-eligible patients is a major limiting factor in organ transplant. Educating health care professionals about their role may lead to measurable improvements in the process. Our aim was to describe the developmental steps of a communication skills training program for health care professionals using standardized patients and to evaluate the results. Materials and Methods: We developed a rubric and 5 cases for standardized family interviews. The 20 participants interviewed standardized families at the beginning and at the end of the training course, with interviews followed by debriefing sessions. Participants also provided feedback before and after the course. The performance of each participant was assessed by his or her peers using the rubric. We calculated the generalizability coefficient to measure the reliability of the rubric and used the Wilcoxon signed rank test to compare achievement among participants. Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 17.0, IBM Corporation, Armonk, NY, USA). Results: All participants received higher scores in their second interview, including novice participants who expressed great discomfort during their first interview. The participants rated the scenarios and the standardized patients as very representative of real-life situations, with feedback forms showing that the interviews, the video recording sessions, and the debriefing sessions contributed to their learning. Conclusions: Our program was designed to meet the current expectations and implications in the field of donor consent from next of kin. Results showed that our training program developed using standardized patient methodology was effective in obtaining the communication skills needed for family interviews during the consent process. The rubric developed during the study was a valid and reliable assessment tool that could be used in further educational activities. The participants showed significant improvements in communication skills

Synthesis of novel 2-[4-(4-substitutedbenzamido/phenylacetamido) phenyl]benzothiazoles as antimicrobial agents

Abstract A new series of 2-[4-(4-substitutedbenzamido/ phenylacetamido)phenyl] benzothiazole derivatives (6a-k) were synthesized and evaluated for antibacterial and antifungal activities against Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli with their drug-resistant isolates and a yeast Candida albicans. Microbiological results indicated that the compounds possessed a broad spectrum of activity against the tested microorganisms at minimum inhibitory concentration (MIC) values between 100 and 6.25 lg/ml. Compounds 6d and 6k exhibited significant antibacterial activity showing 6.25 lg/ml MIC values against drugresistant S. aureus and P. aeruginosa isolates, respectively