Author: Koirala, Suman ; Varshney, Nidhi ; Jha, Hem Chandra ; Kashyap, Dharmendra ; Roy, Rajarshi ; Kar, Parimal ; Samanta, Sunanda ; Bagde, Pranit Hemant ; Saini, Vaishali

Cancer is a condition in which a few of the body's cells grow beyond its control and spread to other outward regions. Globally, gastric cancer (GC) is third most common cause of cancer-related mortality and the fourth most common kind of cancer. Persistent infection of VacA-positive Helicobacter pylori (H. pylori) modulates cellular physiology and leads to GC. About ∼70% of H. pylori are positive for vacuolating cytotoxin-A (VacA), and it infects ∼80-90% of world populations. Herein, for first time, we repurposed FDA-approved gram-negative antibiotics, which are feasible alternatives to existing regimens and may be used in combinatorial treatment against VacA-positive H. pylori. Out of 110 FDA-approved antibiotics, we retrieved 92 structures, which were screened against the VacA protein. Moreover, we determined that the top eight hit antibiotics viz; cefpiramide, cefiderocol, eravacycline, doxycycline, ceftriaxone, enoxacin, tedizolid, and cefamandole show binding free energies of -9.1, -8.9, -8.1, -8.0, -7.9, -7.8, -7.8 and -7.8 Kcal/mol, respectively, with VacA protein. Finally, we performed 100 ns duplicate MD simulations on the top eight selected antibiotics showing strong VacA binding. Subsequently, five antibiotics, including cefiderocol, cefpiramide, doxycycline, enoxacin, and tedizolid show stable ligand protein distance and good binding affinity revealed by the MM-PBSA scheme. Among the five antibiotics cefiderocol act as the most potent inhibitor (-28.33 kcal/mol). Furthermore, we also identified the hotspot residue like Asn-506, Tyr-529, and Phe-483 which control the interaction. Concisely, we identified antibiotics that can be repurposed against VacA of H. pylori and explored their molecular mechanism of interaction with VacA.Communicated by Ramaswamy H. Sarma.

01 Jul 2024·Forensic Toxicology

Liquid chromatography with tandem mass spectrometric method for determination of 52 antibiotics in human whole blood and urine and application to forensic cases

Article

Author: Zhang, Chao ; Wang, Shuhui ; Guo, Zhongyuan ; Yun, Keming ; Wang, Gege ; Wei, Zhiwen ; Zhang, Dan ; Fu, Shanlin ; Shi, Qianwen

PURPOSEA rapid and reliable method was developed and validated for the simultaneous analysis of 52 antibiotics (cephalosporins, penicillins, carbapenems, lincosamides, quinolones, nitroimidazoles, macrolides, sulfonamides, tetracyclines, glycopeptide) in urine and whole blood by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).METHODAnalytes were extracted by dilution or protein precipitation and analyzed on an Agilent 1260 HPLC system coupled to an Agilent 6470 Triple Quadrupole Mass Spectrometer.RESULTSThe method attended method validation criteria. The limits of detection were equal or lower than 2.0 ng/mL, whereas the limits of quantification ranged from 0.1 to 10.0 ng/mL, from 0.1 to 5.0 ng/mL, in urine and whole blood, respectively. For all analytes, the bias and intra- and inter-day precision values were less than 14.7%. The ranges of recovery values of all antibiotics were 76.5-124.5% in whole blood and 76.3-121.8% in urine, values of the effects were lower than 25% in two matrices. No evidence of carryover was observed. The study of sample stability showed that almost all analytes were stable at 24 °C for 24 h, all analytes were stable at -20 °C for 14 days and at -80 °C for 30 days. Freeze-thaw cycles stability showed that antibiotics were stable except for imipenem. Autosampler stability study showed that all analytes were stable for 24 h, except for imipenem and amoxicillin. Applicability was proven by analyzing authentic whole blood (n = 86) and urine (n = 79) samples from patients under antibiotics treatment. Therefore, this method was applied to the analysis 3 forensic allergy cases, which were positive for at least one analyte.CONCLUSIONSA simple, sensitive and high-throughput method for the simultaneous determination of different classes of antibiotics in urine and whole blood samples was developed and applied. This sensitive method was successfully applied to forensic cases.

01 Jun 2024·Molecular Diversity

Repurposing of drug molecules from FDA database against Hepatitis C virus E2 protein using ensemble docking approach

Article

Author: Datta, Joyeeta ; Chaudhuri, Dwaipayan ; Majumder, Satyabrata ; Giri, Kalyan

Hepatitis C virus, a member of the Flaviviridae family and genus Hepacivirus, is an enveloped, positively single stranded RNA virus. Its surface consists of a heterodimer of E1 and E2 proteins which play a crucial role in receptor binding and membrane fusion. In this study we have used in silico virtual screening by utilizing ensemble docking on the approved drugs. These drugs can bind with high efficiency to the 36 prominent conformations of the CD81 binding site clustered from a total of 3 µs MD simulation data on the E2 protein. We started with 9213 compounds from the FDA list of drugs and progressively came down to 5 compounds which have been seen to bind with very high efficiency to not only all the conformations but also the two predicted druggable pockets that encompass the CD81 binding site. MM/PBSA binding energy calculations also point to the highly stable interaction of the compounds to the E2 protein. This study may in future broaden the arsenal of therapeutics for use against HCV infection and lead to more effective care against the virus.

100 Deals associated with Cefpiramide Sodium

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KEGG	Wiki	ATC	Drug Bank
D01904	Cefpiramide Sodium	J01DD11	DB00430

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Indication	Country/Location	Organization	Date
Bacterial Infections	China	Hainan Huluwa Pharmaceutical Group Co., Ltd.	03 Sep 2004
Burns	China	Yuhan Corp.	23 Jul 2004
Laryngitis	China	Yuhan Corp.	23 Jul 2004
Pharyngitis	China	Yuhan Corp.	23 Jul 2004
Sepsis	China	Lek Pharmaceuticals dd	30 Dec 1999

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EULAR2002	Not Applicable	Lupus Nephritis	24	CyA (Group I)	fmnojjzora(sexphegcms) = zvhcxzpypv ccxwiojzvt (pmwdvgdvoe ) View more	-	12 Jun 2002
				CPM (Group II)	fmnojjzora(sexphegcms) = xhodrfjesm ccxwiojzvt (pmwdvgdvoe ) View more

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