Biological investigation of N-methyl thiosemicarbazones as antimicrobial agents and bacterial carbonic anhydrases inhibitors

The enormous burden of the COVID-19 pandemic in economic and healthcare terms has cast a shadow on the serious threat of antimicrobial resistance, increasing the inappropriate use of antibiotics and shifting the focus of drug discovery programmes from antibacterial and antifungal fields. Thus, there is a pressing need for new antimicrobials involving innovative modes of action (MoAs) to avoid cross-resistance rise. Thiosemicarbazones (TSCs) stand out due to their easy preparation and polypharmacological application, also in infectious diseases. Recently, we reported a small library of TSCs (1–9) that emerged for their non-cytotoxic behaviour. Inspired by their multifaceted activity, we investigated the antibacterial, antifungal, and antidermatophytal profiles of derivatives 1–9, highlighting a new promising research line. Furthermore, the ability of these compounds to inhibit selected microbial and human carbonic anhydrases (CAs) was assessed, revealing their possible involvement in the MoA and a good selectivity index for some derivatives.     

Biochemical properties of purified cathepsin B from Schistosoma mansoni

A previously described “major acidic proteinase” of adult Schistosoma mansoni, believed to play a key role in the parasite's metabolism, has been identified as a cathepsin B (Sm31). Purified Sm cathepsin B was not recognized by anti-Sm32 or anticathepsin L antibodies. The enzyme hydrolyzes the synthetic protease substrates Z-Arg-Arg-AMC and Z-Phe-Arg-AMC as well as protein substrates. Its pH optimum is 3.0 with serum albumin, 4.0–5.0 with globin and 5.5–6.0 with the synthetic substrates. The enzyme was inactivated by cysteine proteinase inhibitors. Its activity against protein substrates would support the hypothesis that it plays a role in schistosome nutrition.     

Green micellar spectrofluorimetric determination of α-mangostin found in herbal products as antioxidant and other biological activities beneficial to human health

Pharmaceutical product quality control (QC) needs quick, sensitive and economical procedures to deliver high throughput at low cost, which is the key factor considered by such economic facilities. To lessen the risky effects of research laboratories, researchers must take into account the ecological impacts. α-Mangostin (MAG) exhibit anti-inflammatory, antioxidant, anticancer, anti-allergic, antibacterial, antifungal, antiviral and antimalarial activities. Based on the spectrofluorimetric approach, a novel straightforward, sensitive and environmentally friendly method for MAG determination was developed and validated. Many variables were investigated to improve MAG native fluorescence, including solvent type, buffers, pH and additional surfactants. The best MAG fluorescence sensitivity was found in Britton–Robinson buffer (pH 4) at 450 nm after irradiation at 350 nm in the concentration range of 5–50 ng ml⁻¹. The technique was successfully used to determine the presence of MAG in both its approved dose forms and in samples of spiked human plasma, as per FDA standards for validation. According to their evaluation on two recent greenness criteria (GAPI [Green Analytical Procedure Index] and AGREE [Analytical GREEnness]), the suggested approach has been shown to be environmentally beneficial because it normally uses biodegradable chemicals in solvent-free aqueous phases.     

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) colonization and infection in intravenous and inhalational opiate drug abusers

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen in hospital-acquired and community-acquired infections. We hypothesized that drug abuse is a risk factor for community-acquired MRSA (CA-MRSA) infection, and we employed a rapid multiplex PCR technique for MRSA identification. The study was conducted on MRSA isolates from 60 opiate addicts (intravenous and inhalational drug users) to detect the rate and location of MRSA colonization and infection among them in comparison to 60 non-addict patients and 15 healthy volunteer controls. The proportion of addicts with MRSA colonization (and/or infection) was significantly higher than non-addict patients with MRSA colonization. MRSA colonization was associated with infection in 58% of MRSA-colonized addicts. The MRSA nasal carriage in the addicts was significantly higher than MRSA carriage elsewhere, whether in the addicts group or in the non-addict patients group. Moreover, the nasopharyngeal carriage rate of MRSA among addicts was significantly higher than among the non-addict patients. Increasing the duration of addiction resulted in a significant increase in CA-MRSA colonization in opiate addicts. Both inhalational and intravenous drug use led to significant MRSA colonization in the addict population. In conclusion, this study demonstrated how drug abusers, a high-risk group for infections with MRSA, could be a source or a reservoir of CA-MRSA infection in the non-addict population.     

The role of septal surgery in management of the deviated nose

The deviated nose represents a complex cosmetic and functional problem. Septal surgery plays a central role in the successful management of the externally deviated nose. This study included 260 patients seeking rhinoplasty to correct external nasal deviations; 75 percent of them had various degrees of nasal obstruction. Septal surgery was necessary in 232 patients (89 percent), not only to improve breathing but also to achieve a straight, symmetrical, external nose as well. A graduated surgical approach was adopted to allow correction of the dorsal and caudal deviations of the nasal septum without weakening its structural support to the dorsum or nasal tip. The approach depended on full mobilization of deviated cartilage, followed by straightening of the cartilage and its fixation in the corrected position by using bony splinting grafts through an external rhinoplasty approach.     

Synthesis and biological evaluation of novel 6-nitro-5-substituted aminoquinolines as local anesthetic and anti-arrhythmic agents: molecular modeling study

A series of 6-nitro-5-[1-oxo-2-(substituted amino)ethylamino and 2-(substituted amino)propylamino] quinoline was synthesized and evaluated for their local anesthetic and anti-arrhythmic activity. The detailed synthesis, spectroscopic, and biological data are reported. Molecular modeling methods are used to study the local anesthetic activity of lidocaine and the active compounds by means of the AM1 method. The superposition of the stable conformations of these compounds was studied using the HyperChem 5.11 program.     

Protein solubility, digestibility and fractionation after germination of sorghum varieties

The changes in crude protein, free amino acids, amino acid composition, protein solubility, protein fractionation and protein digestibility after germination of sorghum were investigated. Sorghum varieties (Dorado, Shandaweel-6, Giza-15) were soaked for 20 h followed by germination for 72 h; the results revealed that crude protein and free amino acids in raw sorghum varieties ranged from 10.62 to 12.46% and 0.66 to 1.03 mg/g, respectively. Shandaweel-6 was the highest variety in crude protein and free amino acids content. After germination, crude protein was decreased and free amino acids were increased. There was an increase in content of valine and phenylalanine amino acids after germination. On the other hand, there was a decrease in most of amino acids after germination. After germination protein solubility was significantly increased. Regarding protein fractions, there was an increase in albumin, globulin and kafirin proteins and a decrease in cross linked kafirin and cross linked glutelin after germination.     

Evaluation of the potential cardioprotective activity of some Saudi plants against doxorubicin toxicity

Doxorubicin (DOX) is an anthracycline antibiotic widely used as a chemotherapeutic agent in the treatment of several tumours. However, its cardiac toxicity limits its use at maximum therapeutic doses. Most studies implicated increased oxidative stress as the major determinant of DOX cardiotoxicity. The local Saudi flora is very rich in a variety of plants of quite known folkloric or traditional medicinal uses. Tribulus macropterus Boiss., Olea europaea L. subsp. africana (Mill.) P. S. Green, Tamarix aphylla (L.) H. Karst., Cynomorium coccineum L., Cordia myxa L., Calligonum comosum L' Hér, and Withania somnifera (L.) Dunal are Saudi plants known to have antioxidant activities. The aim of the current study was to explore the potential protective effects of methanolic extracts of these seven Saudi plants against DOX-induced cardiotoxicity in rats. Two plants showed promising cardioprotective potential in the order Calligonum comosum > Cordia myxa. The two plant extracts showed potent in vitro radical scavenging and antioxidant properties. They significantly protected against DOX-induced alterations in cardiac oxidative stress markers (GSH and MDA) and cardiac serum markers (CK-MB and LDH activities). Additionally, histopathological examination indicated a protection against DOX-induced cardiotoxicity. In conclusion, C. comosum and C. myxa exerted protective activity against DOX-induced cardiotoxicity, which is, at least partly, due to their antioxidant effect.     

Plasma neuropeptide Y levels relate cigarette smoking and smoking cessation to body weight regulation

Loss and disproportionate gain of body weight often seen respectively in smokers and quitters are believed to be due to disrupted energy homeostasis induced by nicotine, the major constituent of cigarette smoke. Energy homeostasis is suggested to be regulated by the coordinated actions of peripheral adipose tissue derived leptin and the brain hypothalamic orexigenic neuropeptide Y (NPY). While the studies probing the role of leptin and NPY in weight modulating effect of nicotine have so far been inconsistent and based largely on animal systems, there is a paucity of data involving human subjects. Here we measured the plasma levels of orexigenic neuropeptide Y (NPY) and leptin in 35 non-smokers and 31 cigarette smokers before and three months after smoking cessation. Compared to non-smokers, smokers were leaner and had reduced NPY and leptin levels. Smoking cessation resulted in a significant weight gain and increased waist circumference accompanied by increased leptin and NPY levels. NPY levels were significantly correlated with body weight (r=0.43, p<0.05), BMI (r=0.41, p<0.05), and waist circumference (r=0.37, p<0.05), while leptin correlated with BMI (r=0.42, p<0.05) and waist circumference (r=0.39, p<0.05). Association of leptin with smoking status, but not that of NPY, was lost after controlling for anthropometric parameters. Weight modulating effect of cigarette smoke may thus involve its direct action on NPY, independent of leptin. Altered leptin levels in smokers and quitters may merely reflect changes in body weight or precisely fat mass.     

Cytogenotoxic effects of Adenium obesum seeds extracts on breast cancer cells

The extracts prepared from various areal parts of the Adenium obesum (Forssk.) Roem. & Schult. (Family: Apocynaceae) including leaves, fruit and seeds ethanolic extracts and seed aqueous extract were evaluated against MCF-7 cells in order to investigate its potential of cytogenotoxicity and induction of apoptosis. The ethanolic seeds extract had comparatively higher cytotoxicity (IC₅₀?～?337?µg/ml). Further, apoptosis and DNA damaging potential of seeds ethanolic extract was analyzed by applying multiple sub-lethal concentrations and durations. Flow cytometry results revealed that maximum percentage of early apoptosis (37%) and late apoptosis (35%) were observed after 12?h exposure in concentrations 200?µg/ml and 300?µg/ml, respectively. Similarly, the higher effect of extract in terms of DNA damage by alkaline comet assay was registered after 12?h treatment at concentrations 200 and 300?µg/mL. The calculated total damage score (TDS) for these concentrations were 614 and 617, respectively. The above findings indicate that A. obesum ethanolic seeds extracts has cytogenotoxic properties that could be further explored for the potential source of chemotherapeutic lead against cancer.