Design, synthesis, and computational docking techniques of novel 1,2,3‒triazole‒tetrazole hybrids as potential leads in the development of anticancer agents

Author: Allaka, Tejeswara Rao ; Vudari, Balaraju ; Vellaiyan, Venkatesan ; Nagarajaiah, Honnappa ; Chepuri, Kalyani ; Bhoomandla, Srinu

New flurbiprofen linked 1,2,3-triazole and tetrazole scaffolds have been designed and synthesized using a Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC).All the synthesized compounds were examined for the growth inhibition of HepG2, HuH7, MCF-7, and T-47D tumor cells and binding with focusing on the human cytochrome P 450 2C9 active site was investigated using mol. modeling.There was a strong correlation between the data from the docking studies and the biol. screening results.The cell lines that responded to the novel compound′s effects the best were HepG2 and MCF-7.Compound 5j was the most efficacious derivative among the four cancer cells (HepG2, HuH7, MCF-7, and T-47D) having IC₅₀ values of 1.89 ± 0.103, 2.86 ± 0.167, 1.66 ± 0.056, and 3.55 ± 0.045 μM, resp. and it had greater activity than doxorubicin.In addition, an in silico docking anal. was carried out to confirm the results of the experimentThe results highlight the potential of our triazole-bridged tetrazoles when combined with flurbiprofen (PDB: 1R9O) to enter the active site of human cytochrome P 450 2C9.The proposed binding mode of ligand 5 g was shown three hydrogen bonding via tetrazole with Glu427 (N24...OE1), triazole with Ala280 (N17...O) and fluoro group with Arg80 (F28...NH2) residues their internuclear distances are 2.89 Å, 2.71 Å, and 3.19 Å resp.Furthermore, the ADMET profile was assessed for each mol., and the findings of the in vitro and in silico investigations indicate that the triazoles incorporating tetrazole provide important new information for the creation of innovative anti-cancer treatments.

04 Nov 2024·Journal of Antimicrobial Chemotherapy

Comparative evaluation of early treatment with ceftolozane/tazobactam versus ceftazidime/avibactam for non-COVID-19 patients with pneumonia due to multidrug-resistant Pseudomonas aeruginosa

Article

Author: Watanabe, Alexandre H ; Nathanson, Brian H ; Lodise, Thomas P ; Min, Jae ; Yucel, Emre ; Obi, Engels N

AbstractBackgroundCeftolozane/tazobactam and ceftazidime/avibactam are commonly used in patients with MDR-Pseudomonas aeruginosa (PSA) pneumonia (PNA). This study compared outcomes between non-COVID-19 hospitalized patients with MDR-PSA PNA who received ceftolozane/tazobactam or ceftazidime/avibactam.MethodsThe study included non-COVID-19 adult hospitalized patients with MDR-PSA PNA in the PINC AI Healthcare Database (2016–22) who received ceftolozane/tazobactam or ceftazidime/avibactam within 3 days of index culture for ≥2 days. Outcomes were mortality, recurrent MDR-PSA PNA, discharge destination, post-index culture day length of stay (LOS) and costs (in US dollars, USD), and hospital readmission.ResultsThe final sample included 197 patients (117 ceftolozane/tazobactam, 80 ceftazidime/avibactam). No significant differences were observed in mortality and post-index culture LOS and costs between groups. In the multivariable analyses, patients who received ceftolozane/tazobactam versus ceftazidime/avibactam had lower recurrent MDR-PSA PNA (7.9% versus 18.0%, P = 0.03) and 60 day PNA-related readmissions (11.1% versus 28.5%, P = 0.03) and were more likely to be discharged home (25.8% versus 9.8%, P = 0.03). Compared with ceftazidime/avibactam patients, ceftolozane/tazobactam patients had lower adjusted median total antibiotic costs (5052 USD versus 8099 USD, P = 0.003) and lower adjusted median comparator (ceftolozane/tazobactam or ceftazidime/avibactam) antibiotic costs (3938 USD versus 6441 USD, P = 0.005). In the desirability of outcome ranking (DOOR) analysis, a ceftolozane/tazobactam-treated patient was more likely to have a more favourable outcome than a ceftazidime/avibactam-treated patient [DOOR probability: 59.6% (95% CI: 52.5%–66.8%)].ConclusionsEarly treatment with ceftolozane/tazobactam may offer some clinical and cost benefits over ceftazidime/avibactam in patients with MDR-PSA PNA. Further large-scale studies are necessary to comprehensively understand the outcomes associated with these treatments for MDR-PSA PNA.

01 Jul 2024·International Journal of Biological Macromolecules

Unveiling potential inhibitors targeting the nucleocapsid protein of SARS-CoV-2: Structural insights into their binding sites

Article

Author: Mukherjee, Sulakshana P ; Bihani, Subhash C ; Kumari, Shweta ; Gupta, Gagan D ; Mistry, Hiral

The Nucleocapsid (N) protein of SARS-CoV-2 plays a crucial role in viral replication and pathogenesis, making it an attractive target for developing antiviral therapeutics. In this study, we used differential scanning fluorimetry to establish a high-throughput screening method for identifying high-affinity ligands of N-terminal domain of the N protein (N-NTD). We screened an FDA-approved drug library of 1813 compounds and identified 102 compounds interacting with N-NTD. The screened compounds were further investigated for their ability to inhibit the nucleic-acid binding activity of the N protein using electrophoretic mobility-shift assays. We have identified three inhibitors, Ceftazidime, Sennoside A, and Tannic acid, that disrupt the N protein's interaction with RNA probe. Ceftazidime and Sennoside A exhibited nano-molar range binding affinities with N protein, determined through surface plasmon resonance. The binding sites of Ceftazidime and Sennoside A were investigated using [¹H, ¹⁵N]-heteronuclear single quantum coherence (HSQC) NMR spectroscopy. Ceftazidime and Sennoside A bind to the putative RNA binding site of the N protein, thus providing insights into the inhibitory mechanism of these compounds. These findings will contribute to the development of novel antiviral agents targeting the N protein of SARS-CoV-2.

100 Deals associated with Cefonicid Sodium

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KEGG	Wiki	ATC	Drug Bank
D00912	Cefonicid Sodium	J01DC06	DB01328

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Indication	Country/Location	Organization	Date
Bacterial Infections	China	ACS Dobfar SpA	17 Dec 2001

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