40 research outputs found
Search for gravitational waves associated with gamma-ray bursts detected by Fermi and Swift during the LIGO–Virgo run O3b
Get PDFWe search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC–2020 March 27 17:00 UTC). We conduct two independent searches: a generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate
Photoactivatable prodrug for simultaneous release of mertansine and CO along with a BODIPY derivative as a luminescent marker in mitochondria: a proof of concept for NIR image-guided cancer therapy
No full textControlled and efficient activation is the crucial aspect of designing an effective prodrug. Herein we demonstrate a proof of concept for a light activatable prodrug with desired organelle specificity. Mertansine, a benzoansamacrolide, is an efficient microtubule-targeting compound that binds at or near the vinblastine-binding site in the mitochondrial region to induce mitotic arrest and cell death through apoptosis. Despite its efficacy even in the nanomolar level, this has failed in stage 2 of human clinical trials owing to the lack of drug specificity and the deleterious systemic toxicity. To get around this problem, a recent trend is to develop an antibody-conjugatable maytansinoid with improved tumor/organelle-specificity and lesser systematic toxicity. Endogenous CO is recognized as a regulator of cellular function and for its obligatory role in cell apoptosis. CO blocks the proliferation of cancer cells and effector T cells, and the primary target is reported to be the mitochondria. We report herein a new mitochondria-specific prodrug conjugate (Pro-DC) that undergoes a photocleavage reaction on irradiation with a 400 nm source (1.0 mW cm−2) to induce a simultaneous release of the therapeutic components mertansine and CO along with a BODIPY derivative (BODIPY(PPH3)2) as a luminescent marker in the mitochondrial matrix. The efficacy of the process is demonstrated using MCF-7 cells and could effectively be visualized by probing the intracellular luminescence of BODIPY(PPH3)2. This provides a proof-of-concept for designing a prodrug for image-guided combination therapy for mainstream treatment of cancer
Synthesis and biological evaluation of new fluconazole β-lactam conjugates linked via 1,2,3-triazole
No full textNovel 1,2,3-triazole-linked β-lactam–fluconazole conjugates 12(a–l) were designed and synthesized. The compounds showed potent antifungal activity against two pathogenic Candida strains; Candida albicans ATCC 24433 and Candida albicans ATCC 10231 with MIC values in the range of 0.0625–2 μg mL−1. Compounds 12h, 12j and 12k showed promising antifungal activity against all the tested fungal pathogens except C. neoformans ATCC 34554 compared to fluconazole. Compound 12j in which the β-lactam ring was formed using para-anisidine and benzaldehyde was found to be more potent than fluconazole against all the fungal strains with an IC50 value of <0.015 μg mL−1 for Candida albicans (ATCC 24433). Mechanistic studies for active compounds revealed that the antifungal action was due to ergosterol inhibition. Compounds 12h and 12j at a concentration of 0.125 μg mL−1 caused 91.5 and 96.8% ergosterol depletion, respectively, compared to fluconazole which at the same concentration caused 49% ergosterol depletion. The molecular docking study revealed that all the fluconazole β-lactam conjugates 12(a–l) could snugly fit into the active site of lanosterol 14α-demethylase (CYP51) with varying degrees of affinities. As anticipated, the binding energy for compound 12j (−58.961 kcal mol−1) was much smaller than that for fluconazole (−52.92 kcal mol−1). The synthesized compounds have therapeutic potential for the control of candidemia.</p
Au25 Clusters as Electron-Transfer Catalysts Induced the Intramolecular Cascade Reaction of 2-nitrobenzonitrile
No full textAnti-TB evaluation of novel 2,3-dihydroquinazolin-4(1H)-ones and in silico studies of the active compounds
No full textA direct and simple approach for the synthesis of indole-3-propanol and its acetates from dihydropyran
No full textSynthesis of some new glutamine linked 2,3-disubstituted quinazolinone derivatives as potent antimicrobial and antioxidant agents
No full textEvaluation of antitumor potential of synthesized novel 2-substituted 4-anilinoquinazolines as quinazoline-pyrrole hybrids in MCF-7 human breast cancer cell line and A-549 human lung adenocarcinoma cell lines
No full textComparative biological study between quinazolinyl–triazinyl semicarbazide and thiosemicarbazide hybrid derivatives
No full textDirected ortho-lithiation as a tool for synthesis of chiral 1,2-disubstituted arylsulfonamides
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