Synthesis of Quinazoline and Quinazolinone Derivatives

Active heterocyclic compounds are one of the main topics of interest for the medicinal chemists as they display a number of pharmacological activities. Nitrogen, sulfur, and oxygen containing five- and six-membered heterocyclic compounds have occupied enormous significance in the field of medicinal chemistry. The most important six-membered heterocyclic compounds are quinazoline and quinazolinone derivatives for their biological activities. The current chapter outlined the different methods for synthesis of quinazoline and quinazolinone derivatives that possess broad spectrum of biological activities

A state of the art review of the impact of Vertical Greenery Systems (VGS) on the energy performance of buildings in temperate climates

Rapid urbanization and climate change concerns have led to a growing drive to integrate nature into the built environment. It is expected that London will face increasing risks of flooding, overheating and drought, through hotter drier summers and warmer wetter winters. In response, the Mayor of London adopted new policies for encouraging the use of living roofs and green walls. Greenery systems are considered as promising solutions for improving energy and thermal efficiency of buildings as well as reducing pollution, encouraging biodiversity and water runoff, reducing Urban Heat Island (UHI) effects and improving the microclimate overall. The research aims to review the current state-of-the-art literature concerning the potentials and limitations of vertical greenery systems on energy and thermal performance of buildings in temperate climates. This review paper synthesises and summarizes the literature with regards to vertical green systems (VGS) when used as a passive design strategy to enhance energy savings in buildings. From the review of the literature, some key aspects to consider when designing VGS are outlined, such as climate influence, the plant species grown and the different operating mechanisms as associated such as shade, evapotranspiration, insulation and wind barrier. The results achieved from the literature review clearly indicate that green walls may be considered as key solutions to mitigate operational energy consumption of buildings as well as provide thermally comfortable indoor and outdoor environments. The results of this research will prove useful to builders, architects, engineers and policy makers as it will provide an in-depth understanding of the potential of VGS to mitigate building related energy consumption in a renewable, sustainable, energy-efficient and cost-effective way

Preconcentration and Detection of Gefitinib Anti-Cancer Drug Traces from Water and Human Plasma Samples by Means of Magnetic Nanoparticles

Along of widespread application of anti-cancer drug Gefitinib (GEF), it appears in human body fluids as well as clinical wastewater. Consequently, a reliable and easy-to-adapt detection technique is of essential importance to quantify the drug in different media. The extraction and quantitative detection of anti-cancer drug Gefinitib (GEF) is demonstrated based on a straightforward and efficient magnetic nanoparticle-assisted preconcentration route from water and human plasma samples. Iron oxide magnetic nanoparticles (Fe3O4) have been prepared with an average particle size of 15 nm and utilized as extractible adsorbents for the magnetic solid-phase extraction (MSPE) of GEF in aqueous media. The method is based on MSPE and preconcentration of GEF followed by High-Performance Liquid Chromatography-Ultraviolet Detection (HPLC-UV). The yield of GEF extraction under the optimum MSPE conditions were 94% and 87% for water and plasma samples, respectively. The chromatographic separation was carried out isocratically at 25 °C on a Phenomenex C8 reversed phase column (150 mm × 4.6 mm, with 5 µm particle size). The proposed method was linear over concentration ranges of 15.0–300.0 and 80.0–600.0 ng/mL for water and plasma samples with limits of detection of 4.6 and 25.0 ng/mL in a respective order. Relative standard deviations (%RSD) for intra-day and inter-day were 0.75 and 0.94 for water samples and 1.26 and 1.70 for plasma samples, respectively. Using the magnetic nanoparticles (MNPs) as loaded drug-extractors made the detection of the anti-cancer drug environmentally friendly and simple and has great potential to be used for different drug-containing systems

The influence of urban green systems on the Urban Heat Island effect in London

Urban areas are typically warmer than rural ones. This is mainly due to denser configuration dominated by impermeable surfaces such as buildings and roads, compared to rural areas which are less densely built and mainly dominated by open spaces. Rapid urban expansion in dense cities bares direct impact on surface and air temperature patterns within street canyons; a phenomena which is known as the Urban Heat Island (UHI) effect. Thus, several UK city councils such as Birmingham, Manchester, and London have started to develop strategies aiming at enhancing urban green systems (UGS) through trees, green walls and green roofs. Some of those strategies include considering the green space factor, and increasing green areas within the cities to improve street canyon microclimate and reduce UHI. The Mayor of London has adopted a strategy for London 2050 aspiring to transform it to be the greenest city in the world by increasing the green areas up to 50%. This paper investigates the influence of increasing the UGS percentage which is considered as a key solution to mitigate UHI effect which will, in turn, provide thermally comfortable outdoor environments for pedestrians. The investigation is undertaken by comparing the morphology of precincts and streets in relation to air temperature, mean radiant temperature and surface temperature within Oxford Street canyons in London city centre; being one of the world’s busiest streets. The results from this research demonstrate that different UGS interventions with varying percentage are required depending on particular canyon orientations and geometries. The study found that, in general, more trees would have significant thermal comfort effect followed by living façade, while high albedo pavement (HAP) came last. However, HAP had high influence on improving thermal comfort in North-South orientated streets with minor variance to trees and living facades which, changing their percentage levels was insignificant

Synthesis and antimicrobial study of new tetrazole, benzimidazole and N3-functionalized quinazolinone derivatives

Reactions of 4H-3,1-benzoxazin-4-one 3 with various nitrogen nucleophiles; sodium azide, hydroxylamine hydrochloride, ammonium acetate, and formamide afforded new N-heterocyclic compounds 4-7. The synthesized quinazolinone derivative 7 was used as a useful building block for further synthesis of new series of N3-functionalized quinazolinone compounds 8-12. The chemical structures of all synthesized heterocyclic compounds were deduced from their spectroscopic analyses. The antimicrobial activity of the new compounds was evaluated against several pathogenic microorganisms, and most of them showed remarkable activity comparable to the antibacterial Ciprofloxacin and antifungal Clotrimazole

Nanoparticles of a pyrazolo-pyridazine derivative as potential EGFR and CDK-2 inhibitors: design, structure determination, anticancer evaluation and in silico studies

The strategic planning of this study is based upon using the nanoformulation method to prepare nanoparticles 4-SLNs and 4-LPHNPs of the previously prepared 4,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-3-amine (4) after confirming its structure with single crystal X-ray analysis. These nanoparticles exhibited promising cytotoxic activity against HepG-2, HCT-116 and MCF-7 cancer cell lines in comparison with the reference doxorubicin and the original derivative 4. Moreover, their inhibitory assessment against EGFR and CDK-2/cyclin A2 displayed improved and more favorable impact than the parent 4 and the references. Detection of their influence upon cancer biomarkers revealed upregulation of Bax, p53 and caspase-3 levels and downregulation of Bcl-2 levels. The docking simulation demonstrated that the presence of the pyrazolo[3,4-c]pyridazin-3-amine scaffold is amenable to enclosure and binding well within EGFR and CDK-2 receptors through different hydrophilic interactions. The pharmacokinetic and physicochemical properties of target 4 were also assessed with ADME investigation, and the outcome indicated good drug-like characteristics

Characterizing the morbid genome of ciliopathies

Background Ciliopathies are clinically diverse disorders of the primary cilium. Remarkable progress has been made in understanding the molecular basis of these genetically heterogeneous conditions; however, our knowledge of their morbid genome, pleiotropy, and variable expressivity remains incomplete. Results We applied genomic approaches on a large patient cohort of 371 affected individuals from 265 families, with phenotypes that span the entire ciliopathy spectrum. Likely causal mutations in previously described ciliopathy genes were identified in 85% (225/265) of the families, adding 32 novel alleles. Consistent with a fully penetrant model for these genes, we found no significant difference in their “mutation load” beyond the causal variants between our ciliopathy cohort and a control non-ciliopathy cohort. Genomic analysis of our cohort further identified mutations in a novel morbid gene TXNDC15, encoding a thiol isomerase, based on independent loss of function mutations in individuals with a consistent ciliopathy phenotype (Meckel-Gruber syndrome) and a functional effect of its deficiency on ciliary signaling. Our study also highlighted seven novel candidate genes (TRAPPC3, EXOC3L2, FAM98C, C17orf61, LRRCC1, NEK4, and CELSR2) some of which have established links to ciliogenesis. Finally, we show that the morbid genome of ciliopathies encompasses many founder mutations, the combined carrier frequency of which accounts for a high disease burden in the study population. Conclusions Our study increases our understanding of the morbid genome of ciliopathies. We also provide the strongest evidence, to date, in support of the classical Mendelian inheritance of Bardet-Biedl syndrome and other ciliopathies

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