Efficacy of 5-(2-aroyl)aryloxy methyl-2-phenyl-1,3,4-oxadiazoles as antibacterial and antifungal agents

Research and development of potent and effective antimicrobial agents represent one of the most important advances in therapeutics; the main aim of these efforts is not only control the serious infections, but also prevention and treatment of some infectious complications of other therapeutic modalities. A series of 5-(2-aroyl)aryloxy methyl-2-phenyl-1,3,4-oxadiazoles were screened for their antibacterial and antifungal activities. Anti-bacterial activity against B. cereus, S. aureus, B. subtilis, S. aureus (MRSA), E. aerogenes, M. luteus, K. pneumonia, P. aeruginosa, S. typhimurium, E. coli, paratyphi-B, P. vulgaris bacterial strains and anti-fungal activity against C. albicans, A.niger, F.solani, A.flavus, B.cinerea, C.krusei, M. pachydermatis, C.parapsilosis, F.moniliforme, C.gloeosporioides fungal strains were carried out. The bioassays indicated that most of the synthesized compounds showed potential antibacterial and anti-fungal activity

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

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Structural studies of a novel bioactive benzophenone derivative: (4-Chloro-2-hydroxy-phenyl)-phenyl-methanone

The title compound (4-Chloro-2-hydroxy-phenyl)-phenyl-methanone was synthesized and the product obtained was characterized by spectroscopic techniques, and finally the structure was confirmed by X-ray diffraction studies. The compound crystallizes in the orthorhombic crystal system with the space group Pbca with unit cell parameters, a = 14.0359(5) Å, b = 6.8084(3) Å, c = 23.1097(8) Å, and Z = 4. The structure exhibits an intramolecular hydrogen bond which closes an S(6) ring. No directional interactions beyond the van der Waals packing contacts were identified in the crystal structur

In vitro antibacterial and antifungal evaluation of some benzophenone analogues

Antibacterial and antifungal agents are widely used in the management of infectious disease but most of them have developed resistance to micro-organism. To overcome this problem and to lower the side effects, many approaches can be utilized. Benzophenone derivatives are reported to have the broad spectrum of biological activities. In the present study we have screened benzophenone derivatives 5a-k against six bacterial species viz gram positive (Bacillus subtilis and Staphylococcus aureus) and gram negative (Pseudomonas aeruginosa, Salmonella typhi, Proteus vulgaris, Shigella flexneri) bacteria. Also compounds 5a-k were tested with six fungal species viz (Candida albicans, Aspergillus niger, Fusarium solani, Aspergillus flavus, Botrytis cinerea, Candida krusei). The obtained results showed that the synthesized compounds 5a-k exhibited moderate to good activities against all the tested strains. Compounds 5a, 5c, 5d, 5f and 5g have shown good antibacterial and antifungal activities against selected strains

4-Chloro-2-(2-chlorobenzoyl)phenol

In the title mol¬ecule, C13H8Cl2O2, the dihedral angle between the benzene rings is 74.53 (9)°. An intra¬molecular O-H O hydrogen bond leading to a S(6) ring is observed. In the crystal, the mol-ecules are connected into a three-dimensional network by C-H O and - [inter-centroid distance = 3.6254 (10) Å] inter¬actions

Design and synthesis of diamide-coupled benzophenones as potential anticancer agents

A series of diamide-coupled benzophenone, 2-(4-benzoyl-phenoxy)-N-2-2-(4-benzoyl-phenoxy)-acetylamino-phenyl-acetamide analogues (9a-l) were synthesized by multistep reactions and all compounds were well characterized. Among the series (9a-l), compound 9k with three methyl groups at ortho position in rings A, B, and D and bromo group at the para position in ring E was selected as a lead compound by screening through multiple cancer cell types by in-vitro cytotoxic and antiproliferative assay systems. Also, the cytotoxic nature of the compound 9k resulted the regression of the tumor growth in-vivo, which could be due to decreased vascularisation in the peritoneum lining of the mice which regress the tumor growth. The results were reconfirmed in-vivo chorioallantoic membrane model which indicates a scope of developing 9k into potent anticancer drug in near future