Design, Synthesis and Molecular Docking Studies of Some Novel Spiro Derivatives By 1,3-Cycloaddition Reaction

Synthesis of polycyclic compounds having spiro nucleus has attracted the attention of synthetic organic chemists because of their highly pronounced biological activities such as antiviral, antimicrobial etc. Therefore, the development of new, rapid, and clean synthetic routes of such compounds is of great importance to both medicinal and synthetic chemists. The 1,3-dipolarcycloaddition reactions are proved to be an efficient method for regio and stereo selective synthesis of structurally complex spiro heterocycles from relatively simple precursors. Molecular docking provides a consistent and more precise picture of the interaction of biologically active molecules at the receptor level thereby facilitating the designing of novel therapeutic agents. Therefore, potency of the spiro compounds (4i) was evaluated preliminary through the molecular docking studies. Later substitutions were made in the reference molecule to get the potent compounds

Chitosan-modified nanocarriers as carriers for anticancer drug delivery: promises and hurdles

With the advent of drug delivery, various polymeric materials are being explored to fabricate numerous nanocarriers. Each polymer is associated with a few characteristics attributes which further facilitate its usage in drug delivery. One such polymer is chitosan (CS), which is extensively employed to deliver a variety of drugs to various targets, especially to cancer cells. The desired properties like biological origin, bio-adhesive, biocompatibility, the scope of chemical modification, biodegradability and controlled drug release make it a highly rough after polymer in pharmaceutical nanotechnology. The present review attempts to compile various chemical modifications on CS and showcase the outcomes of the derived nanocarriers, especially in cancer chemotherapy and drug delivery

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

<span style="font-size:10.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-bidi-font-family: Mangal;mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language: HI" lang="EN-US">Design, synthesis and anticonvulsant activity of some newer 3<i style="mso-bidi-font-style:normal">H</i>-quinazolin-4-one derivatives</span>

597-604In the present investigation, a series of 2-[2-(aryl)-2-oxo-ethylsulfanyl]-3-(aryl/propyl)-3H-quinazolin-4-ones have been synthesized and tested for their potential against seizures in mice. All the newly synthesized compounds show moderate to high protection against 6 Hz partial seizure with compound 2b, 2-(2-oxo-2-p-tolyl-ethylsulfanyl)-3-phenyl-3H-quinazolin-4-one emerging as the most active anticonvulsant agent endowed with neuroprotective effect against NMDA and kainate induced excitotoxicity. The results of whole brain GABA assay indicates that the seizure protective activity of <b style="mso-bidi-font-weight: normal">2b can be either due to the increased brain GABA level or due to neuroprotective action

Synthesis and antimicrobial activity of pyrazolinone and pyrazole analogues containing quinoline moiety

1493-1499A new class of quinoline derivatives containing pyrazoline-5-one and pyrazole moiety (<b style="mso-bidi-font-weight: normal">3a-j and 4a-j) have been synthesized by condensation of various oxobutyrates/pentane-2,4-dione derivatives with 8-quinolinoxyacetic acid hydrazide. Elemental analysis, IR, 1H NMR and mass spectral data support the structures of the newly synthesized compounds. The synthesized compounds have been evaluated for their antimicrobial activity against S. aureus, E. coli, A. niger and C. albicans using serial plate dilution method. Compound 4-(2-(4-fluorophenyl)hydrazono)-3-methyl-1-(2-(quinolin-8-yloxy) acetyl)-1H-pyrazol-5(4<i style="mso-bidi-font-style: normal">H)-one 3f having log P 1.52 has emerged as the most potent antimicrobial agent of the series. </span

ChemInform Abstract: Synthesis and Antimicrobial Activity of Pyrazolinone and Pyrazole Analogues Containing Quinoline Moiety.

1493-1499A new class of quinoline derivatives containing pyrazoline-5-one and pyrazole moiety (<b style="mso-bidi-font-weight: normal">3a-j and 4a-j) have been synthesized by condensation of various oxobutyrates/pentane-2,4-dione derivatives with 8-quinolinoxyacetic acid hydrazide. Elemental analysis, IR, 1H NMR and mass spectral data support the structures of the newly synthesized compounds. The synthesized compounds have been evaluated for their antimicrobial activity against S. aureus, E. coli, A. niger and C. albicans using serial plate dilution method. Compound 4-(2-(4-fluorophenyl)hydrazono)-3-methyl-1-(2-(quinolin-8-yloxy) acetyl)-1H-pyrazol-5(4<i style="mso-bidi-font-style: normal">H)-one 3f having log P 1.52 has emerged as the most potent antimicrobial agent of the series. </span

An overview of ion channels therapeutics in the treatment of pain

Significance of the study: The clinical management of severe and chronic pain relies heavily on opioids that cause serious side-effects. There therefore exists an urgent need to develop safer and effective analgesics. Moreover, there has been significant progress in the understanding of pain physiology, especially the role of some ion channels in the pain process. Thus, the immense potential of ion channel therapeutics in pain management is a subject of current interest. Aim of the study: This study is a comprehensive review, focused on ion channels as potential therapeutic targets for the treatment of pain. Research methodology: A systemic search of available literature on ion channels analgesics was performed. Articles related to the drug discovery and clinical trials on relevant topics were extracted from PubMed and other databases. Major conclusion of the study: Small molecules targeted at ion channels pathways hold great promise for creating a new approach to pain treatment. Several molecules targeting TRPV1, TRPV3, TRPV4, TRPA1, TRPM8, Nav1.7, Nav1.8, CaV2.2, CaV3.2, ASIC, and P2X3 have demonstrated potential clinical benefits. However, till date US FDA has approved capsaicin, ziconotide, and pregabalin for the treatment of different pain conditions. This review highlights the possibilities for discovery and research on ion channels and their potential for pain treatment

3,5-Bis(arylidene)-4-piperidones as potential dengue protease inhibitors

Dengue is a severe mosquito-borne viral in fection causing half a million deaths annually. Dengue virusNS2B/NS3 protease is a validated target for anti-dengue drug design. A series of hitherto unreported 3,5-bis(arylidene)-4-piperidones analogues 4a–4j were synthesized and screened in silico against DENV2 NS2B/NS3 protease to elucidate their binding mechanism and orientation around the active sites. Results were validated through an in vitro DENV2 NS2B/NS3 protease assay using a fluorogenic Boc-Gly-Arg-Arg-AMC substrate. Nitro derivatives of 3,5-is(arylidene)-4-piperidones(4e and 4j) merged as promising lead molecules for novel protease inhibitors with an IC50 of 15.22 and 16.23 umoI/L, respectively, compared to the standard, panduratin A, having IC50 of 57.28 umoI/L