Analgesic and anti-inflammatory activities of salicylaldehyde 2-chlorobenzoyl hydrazone (H2LASSBio-466), salicylaldehyde 4-chlorobenzoyl hydrazone (H 2LASSBio-1064) and their zinc(II) complexes

Salicylaldehyde 2-chlorobenzoyl hydrazone (H 2LASSBio-466), salicylaldehyde 4-chlorobenzoyl hydrazone (H 2LASSBio-1064) and their complexes [Zn(LASSBio- 466)H 2O] 2 (1) and [Zn(HLASSBio-1064)Cl] 2 (2) were evaluated in animal models of peripheral and central nociception, and acute inflammation. All studied compounds significantly inhibited acetic acid-induced writhing response. Upon coordination the antinociceptive activity was favored in the complex 1. H 2LASSBio-466 inhibited only the first phase of the formalin test, while 1 was active in the second phase, like indomethacin, indicating its ability to inhibit nociception associated with the inflammatory response. Hence coordination to zinc(II) altered the pharmacological profile of H 2LASSBio-466. H2LASSBio-1064 inhibited both phases but this effect was not improved by coordination. The studied compounds did not increase the latency of response in the hot plate model, indicating their lack of central anti-nociceptive activity. All compounds showed levels of inhibition of zymosan-induced peritonitis comparable or superior to indomethacin, indicating an expressive anti-inflammatory profile.Facultad de Ciencias Exacta

Preliminary in vitro evaluation of the anti-proliferative activity of guanylhydrazone derivatives

Guanylhydrazones have shown promising antitumor activity in preclinical tumor models in several studies. In this study, we aimed at evaluating the cytotoxic effect of a series of synthetic guanylhydrazones. Different human tumor cell lines, including HCT-8 (colon carcinoma), MDA-MB-435 (melanoma) and SF-295 (glioblastoma) were continuous exposed to guanylhydrazone derivatives for 72 hours and growth inhibition of tumor cell lines and macrophages J774 was measured using tetrazolium salt (MTT) assay. Compounds 7, 11, 16 and 17 showed strong cytotoxic activity with IC50 values lower than 10 μmol L–1 against four tumor cell lines. Among them, 7 was less toxic to non-tumor cells. Finally, the obtained data suggest that guanylhydrazones may be regarded as potential lead compounds for the design of novel anticancer agents

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Analgesic and Anti-Inflammatory Activities of Salicylaldehyde 2-Chlorobenzoyl Hydrazone (H(2)LASSBio-466), Salicylaldehyde 4-Chlorobenzoyl Hydrazone (H(2)LASSBio-1064) and Their Zinc(II) Complexes

Salicylaldehyde 2-chlorobenzoyl hydrazone (H(2)LASSBio-466), salicylaldehyde 4-chlorobenzoyl hydrazone (H(2)LASSBio-1064) and their complexes [Zn(LASSBio-466) H(2)O](2) (1) and [Zn(HLASSBio-1064) Cl](2) (2) were evaluated in animal models of peripheral and central nociception, and acute inflammation. All studied compounds significantly inhibited acetic acid-induced writhing response. Upon coordination the anti-nociceptive activity was favored in the complex 1. H(2)LASSBio-466 inhibited only the first phase of the formalin test, while 1 was active in the second phase, like indomethacin, indicating its ability to inhibit nociception associated with the inflammatory response. Hence coordination to zinc(II) altered the pharmacological profile of H(2)LASSBio-466. H(2)LASSBio-1064 inhibited both phases but this effect was not improved by coordination. The studied compounds did not increase the latency of response in the hot plate model, indicating their lack of central anti-nociceptive activity. All compounds showed levels of inhibition of zymosan-induced peritonitis comparable or superior to indomethacin, indicating an expressive anti-inflammatory profile.CNPq, INCT-INOFAR[573.364/2008-6]FAPESP (Brazil)CONICET (Argentina

Chemical constituents from Sidastrum paniculatum and evaluation of their leishmanicidal activity

AbstractSidastrum paniculatum (L.) Fryxell, Malvaceae, is popularly known in Brazil as “malva-roxa” or “malvavisco”. The species is found mainly in Northeast region where it is used by locals to treat spider bites and bee stings. Aiming to identify the chemical compounds from S. paniculatum secondary metabolism and to contribute to the chemotaxonomic knowledge of Malvaceae family, a phytochemical study of S. paniculatum was carried out. Besides that, the isolated compounds were evaluated for antileishmanial activity against promastigotes of Leishmania braziliensis. By using chromatographic techniques the study resulted the isolation of eight compounds: 3-oxo-21β-H-hop-22(29)-ene; sebiferic acid; sitosterol 3-O-β-d-glucopyranoside/stigmasterol 3-O-β-d-glucopyranoside; phaeophytin a; 132(S)-hydroxyphaeophytin a; 132(S)-hydroxy-(173)-ethoxyphaeophorbide a and 7,4′-di-O-methylisoescutellarein. The structure of all isolated compounds was elucidated by spectroscopic analysis, including two-dimensional NMR techniques. In addition, the isolated compounds phaeophytin a; 132(S)-hydroxyphaeophytin a; 132(S)-hydroxy-(173)-ethoxyphaeophorbide a and 7,4′-di-O-methylisoescutellarein exhibited antileishmanial activity against promastigotes of L. braziliensis