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Article ; Online: Synthesis and Anti-cancer Activity of Novel Thiazolidinone Analogs of 6-Aminoflavone.

Moorkoth, Sudheer

2015 Volume 63, Issue 12, Page(s) 974–985

Abstract: Novel heterocyclic analogs were synthesized by combining a flavone nucleus and thiazolidinone ring in an effort to potentiate the existing anti-cancer activity of flavone. The syntheses of 6-aminoflavone, 6-amino-3-methoxyflavone, 6-amino-3-methoxy-3',4'- ...

Abstract	Novel heterocyclic analogs were synthesized by combining a flavone nucleus and thiazolidinone ring in an effort to potentiate the existing anti-cancer activity of flavone. The syntheses of 6-aminoflavone, 6-amino-3-methoxyflavone, 6-amino-3-methoxy-3',4'-dimethxyflavone and their corresponding thiazolidinone analogs were performed. Fifteen novel analogs were synthesized and evaluated for their anti-cancer activity using cell-based assay techniques and in vivo testing. As expected, the analogs improved cytotoxicity and were shown to increase the life span of cancer-bearing mice. Cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays in HeLa, MDA-MB-435, and Vero cell lines. In vivo evaluation of anti-cancer activity performed in albino mice bearing Dalton's ascites carcinoma showed that the new analogs enhanced life span and prevented increases in body weight owing to tumor volumes. Moreover, cell-cycle analysis and Hoechst staining analysis proved the apoptotic potential of these analogs. Preliminary pharmacokinetic evaluation was carried out on the synthesized compounds to determine the lipophilicity and pKa. Lipophilicity was determined using high-performance liquid chromatography and the results showed a direct correlation between the observed anti-cancer activity and log P value, while pKa values indicated the ionizing range which is a prediction tool for solubility and permeability.
MeSH term(s)	Animals ; Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Body Weight/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cercopithecus aethiops ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; Flavonoids/chemistry ; Flavonoids/pharmacology ; HeLa Cells ; Humans ; Mice ; Molecular Structure ; Neoplasms, Experimental/drug therapy ; Neoplasms, Experimental/pathology ; Structure-Activity Relationship ; Thiadiazoles/chemical synthesis ; Thiadiazoles/chemistry ; Thiadiazoles/pharmacology ; Vero Cells
Chemical Substances	Antineoplastic Agents ; Flavonoids ; Thiadiazoles ; aminoflavone (2EXS38428U)
Language	English
Publishing date	2015
Publishing country	Japan
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	213307-6
ISSN	1347-5223 ; 0009-2363
ISSN (online)	1347-5223
ISSN	0009-2363
DOI	10.1248/cpb.c15-00454
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Article ; Online: Validated HPLC method for ceftriaxone from dried blood spots for pharmacokinetic studies and therapeutic drug monitoring in neonatal population.

Chaudhari, Bhim B / Devadiga, Bhagyashree H / Matcha, Saikumar / Lewis, Leslie Es / Mallayasamy, Surulivelrajan / Moorkoth, Sudheer

Bioanalysis

2023 Volume 15, Issue 8, Page(s) 449–463

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Infant, Newborn ; Humans ; Chromatography, High Pressure Liquid/methods ; Ceftriaxone/pharmacokinetics ; Drug Monitoring/methods ; Dried Blood Spot Testing/methods ; Methanol ; Reproducibility of Results
Chemical Substances	Ceftriaxone (75J73V1629) ; Methanol (Y4S76JWI15)
Language	English
Publishing date	2023-05-22
Publishing country	England
Document type	Journal Article
ISSN	1757-6199
ISSN (online)	1757-6199
DOI	10.4155/bio-2023-0047
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Article ; Online: Predictive Performance of Population Pharmacokinetic Models for Amikacin in Term Neonates.

Matcha, Saikumar / Dillibatcha, Jayashree / Raju, Arun Prasath / Chaudhari, Bhim Bahadur / Moorkoth, Sudheer / Lewis, Leslie E / Mallayasamy, Surulivelrajan

Paediatric drugs

2023 Volume 25, Issue 3, Page(s) 365–375

Abstract: Background and objective: Amikacin is preferred in treating Gram-negative infections in neonates and it has a narrow therapeutic window. The population pharmacokinetic modeling approach can aid in designing optimal dosage regimens for amikacin in ... ...

Abstract	Background and objective: Amikacin is preferred in treating Gram-negative infections in neonates and it has a narrow therapeutic window. The population pharmacokinetic modeling approach can aid in designing optimal dosage regimens for amikacin in neonates. In this study, we attempted to identify the suitable population pharmacokinetic model from the published reports for the study population from an Indian setting. Methods: Published population pharmacokinetic studies for amikacin in neonates were identified. Data on structural models and typical pharmacokinetic parameters were extracted from the studies. For the clinical study, neonates who met the inclusion criteria were enrolled in the study from the NICU, Kasturba Medical College, Manipal, during Jan 2020 to March 2022. Drug concentrations were estimated, and demographic and clinical data were collected. Identified population pharmacokinetic models were used to predict the amikacin concentrations in neonates. Predicted concentrations were compared against the observed concentrations. Differences between predicted and observed concentrations were quantified using statistical measures. The population pharmacokinetic model, which was able to predict the data well, is considered a suitable model for the study population. Dosing regimens were suggested for neonates using the pharmacometric simulation approach generated by the selected model. Results: A total of 43 plasma samples were collected from 31 neonates. Twelve population pharmacokinetic models were found for amikacin in neonates. The predictive performance of the 12 studies was performed using clinical data. A two-compartment model reported by Illamola et al. predicted the amikacin concentrations better than other models. Illamola et al. reported creatinine clearance and body weight as the significant covariates impacting the pharmacokinetic parameters of amikacin. This model was able to predict the clinical data with 29.97% and 0.686 of relative median absolute prediction error and relative root mean square error, respectively, which is the best among the published models. The Illamola et al. model was selected as the final model to perform pharmacometric simulations for the subjects with different combinations of creatinine clearance and body weight. Dosage regimens were designed to attain target therapeutic concentrations for the virtual subjects and a nomogram was developed. Conclusions: The population pharmacokinetic model reported by the Illamola et al. model was selected as the final model to explain the clinical data with the lowest relative median absolute prediction error and relative root mean square error when compared with other models. An amikacin nomogram was developed for the neonates whose creatinine clearance and body weight ranged between 10 and 90 mL/min and between 2 and 4 kg, respectively. A developed nomogram can assist clinicians to design an optimal dosage regimen of amikacin for term neonates.
MeSH term(s)	Infant, Newborn ; Humans ; Amikacin ; Anti-Bacterial Agents/therapeutic use ; Creatinine ; Body Weight ; Models, Biological
Chemical Substances	Amikacin (84319SGC3C) ; Anti-Bacterial Agents ; Creatinine (AYI8EX34EU)
Language	English
Publishing date	2023-03-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1492748-2
ISSN	1179-2019 ; 1174-5878
ISSN (online)	1179-2019
ISSN	1174-5878
DOI	10.1007/s40272-023-00564-z
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Article ; Online: Validation of an HPLC method for estimation of cefotaxime from dried blood spot: alternative to plasma-based PK evaluation in neonates.

Chaudhari, Bhim Bahadur / Sridhar, Priyanka / Moorkoth, Sudheer / Lewis, Leslie E / Mallayasamy, Surulivelrajan

Bioanalysis

2021

Abstract: Aim: ...

Abstract	Aim:
Language	English
Publishing date	2021-09-02
Publishing country	England
Document type	Journal Article
ISSN	1757-6199
ISSN (online)	1757-6199
DOI	10.4155/bio-2021-0130
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Article: Bioanalytical method development and validation of highly selective and sensitive LC-MS/MS method for determination of teriparatide (parathyroid hormone fragment 1–34) in human serum through direct detection of intact teriparatide molecule

Kusuma, Manoj Bob / Kashibhatta, Ravisekhar / Gavande, Anil / Kiran, Ravi / Jagtap, Sandeep / Vithala, Praveen / Moorkoth, Sudheer / Bhat, Krishnamurthy

Journal of chromatography. 2021 Dec. 15, v. 1187

2021

Abstract: Teriparatide is a novel recombinant peptide fragment of the first 1–34 amino acids of human parathyroid recommended for treatment of osteoporosis. Therapeutic proteins and peptides are routinely estimated using ligand binding assay formats however LC-MS/ ... ...

Abstract	Teriparatide is a novel recombinant peptide fragment of the first 1–34 amino acids of human parathyroid recommended for treatment of osteoporosis. Therapeutic proteins and peptides are routinely estimated using ligand binding assay formats however LC-MS/MS technique which is routinely used in bioanalysis of small molecules has now gained importance in large molecule bioanalysis for the advantages it can offer over LBAs in terms of improved accuracy, selectivity and anti-body free method development. This paper presents a sensitive bioanalytical method for determination of teriparatide in human serum using ultra performance liquid chromatography aligned with tandem mass spectrometric detection. Teriparatide was isolated from human serum using solid phase extraction. The intact peptide was separated on a chromatograph and the multiply charged ion (+7) was detected using a mass spectrometer. The total run time was 4.0 min. The internal standard used was rat PTH 1–34 fragment. The mass transitions of m/z 589.3 > 656.3 for teriparatide and m/z 677.4 > 778.6 for internal standard were used for MS/MS detection. The sample extraction involved a solid phase extraction method followed by concentration of the eluent by evaporation and subsequent reconstitution. The non-specific binding effect caused by the adherence of the peptides/proteins to the vials/tube walls was significantly reduced by using BSA solution as blocking agent. The method has been validated over a linear range of 15.07–913.3 pg/mL with a correlation coefficient ≥ 0.99. The precision (%RSD) was 6.36 to 10.85 and accuracy was within 96.71% to 100.88%. A two-treatment, two-period, cross over study was conducted to establish bioequivalence between test and reference formulation (20 mcg/80 mL – solution for injection) and the method was successfully applied to quantify teriparatide in serum samples of this clinical study and about 1220 human serum samples were analyzed to determine teriparatide. This method is a promising anti-body free LC-MS/MS based methodology for estimation of teriparatide in human serum and may be applied as starting method for other such peptide molecules.
Keywords	blood serum ; evaporation ; humans ; ligands ; osteoporosis ; parathyroid hormone ; pharmacokinetics ; rats ; recombinant peptides ; solid phase extraction ; spectrometers ; therapeutics ; ultra-performance liquid chromatography
Language	English
Dates of publication	2021-1215
Publishing place	Elsevier B.V.
Document type	Article
ISSN	1570-0232
DOI	10.1016/j.jchromb.2021.123046
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Corrigendum to "A selective and sensitive UPLC-ESI-MS/MS method for quantification of Pegylated Interferon Alfa-2b in human serum using signature peptide-based quantitation" [J. Chromatogr. B 1180 (2021) 122883].

Kusuma, Manoj Bob / Kashibhatta, Ravisekhar / Jagtap, Sandeep S / Nadawade, Vijay / Adsul, Suresh / Moorkoth, Sudheer / Bhat, Krishnamurthy / Mody, Rustom / Vithala, Praveen

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

2022 Volume 1192, Page(s) 123159

Language	English
Publishing date	2022-02-10
Publishing country	Netherlands
Document type	Published Erratum
ZDB-ID	1180823-8
ISSN	1873-376X ; 0378-4347 ; 1570-0232 ; 1387-2273
ISSN (online)	1873-376X
ISSN	0378-4347 ; 1570-0232 ; 1387-2273
DOI	10.1016/j.jchromb.2022.123159
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Article ; Online: Corrigendum to "Bioanalytical method development and validation of highly selective and sensitive LC-MS/MS method for determination of teriparatide (parathyroid hormone fragment 1-34) in human serum through direct detection of intact teriparatide molecule" [J. Chromatogr. B 1187 (2021) 123046].

Kusuma, Manoj Bob / Kashibhatta, Ravisekhar / Gavande, Anil / Kiran, Ravi / Jagtap, Sandeep / Vithala, Praveen / Moorkoth, Sudheer / Bhat, Krishnamurthy

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

2022 Volume 1192, Page(s) 123158

Language	English
Publishing date	2022-02-10
Publishing country	Netherlands
Document type	Published Erratum
ZDB-ID	1180823-8
ISSN	1873-376X ; 0378-4347 ; 1570-0232 ; 1387-2273
ISSN (online)	1873-376X
ISSN	0378-4347 ; 1570-0232 ; 1387-2273
DOI	10.1016/j.jchromb.2022.123158
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Article ; Online: In vitro antibacterial activity and in vivo pharmacokinetics of intravenously administered Amikacin-loaded Liposomes for the management of bacterial septicaemia.

Maxwell, Amala / Chaudhari, Bhim Bahadur / Chaudhari, Pinal / Ananthamurthy, Koteshwara / Aranjani, Jesil / Moorkoth, Sudheer / Ghate, Vivek / Lewis, Shaila

Colloids and surfaces. B, Biointerfaces

2022 Volume 220, Page(s) 112892

Abstract: Systemic delivery of amikacin is a widely adopted treatment modality for severe infections like sepsis. However, the current course of treatment requires repeated bolus doses of amikacin, prolonged hospitalization, and continuous therapeutic monitoring ... ...

Abstract	Systemic delivery of amikacin is a widely adopted treatment modality for severe infections like sepsis. However, the current course of treatment requires repeated bolus doses of amikacin, prolonged hospitalization, and continuous therapeutic monitoring to manage the severe adverse effects. Amikacin has short half-life, which further challenges the delivery of sufficient systemic concentrations when administered by intravenous route. To solve this issue, novel delivery systems, amikacin liposomes (Ak-lip) were developed and evaluated for its antibacterial efficacy (agar plate diffusion and resazurin microtiter assay) and in vivo drug release in Sprague-Dawley rats. The Ak-lip were prepared by modified thin film hydration method and optimized based on particle size and Zeta potential. The zone of inhibition for Ak-lip and amikacin was found to be 22 mm and 26 mm against Staphylococcus aureus. The minimum inhibitory concentrations (MIC) of amikacin and Ak-lip against Staphylococcus aureus were found to be 3 µg/mL and 9 µg/mL, and for Pseudomonas aeruginosa were 0.6 µg/mL and 0.9 µg/mL respectively. The in vivo pharmacokinetic parameters were determined using Gastroplus™. A significant difference in the pharmacokinetic parameters (AUC, C
MeSH term(s)	Rats ; Animals ; Amikacin/pharmacology ; Liposomes/pharmacology ; Rats, Sprague-Dawley ; Anti-Bacterial Agents ; Microbial Sensitivity Tests ; Pseudomonas aeruginosa ; Staphylococcus aureus ; Staphylococcal Infections/drug therapy ; Sepsis/drug therapy
Chemical Substances	Amikacin (84319SGC3C) ; Liposomes ; Anti-Bacterial Agents
Language	English
Publishing date	2022-09-30
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1500523-9
ISSN	1873-4367 ; 0927-7765
ISSN (online)	1873-4367
ISSN	0927-7765
DOI	10.1016/j.colsurfb.2022.112892
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Article ; Online: Biomarker profiling of vitamin responsive seizures: a potential tool to detect pediatric seizures of unknown aetiology.

Mathew, Elizabeth Mary / Moorkoth, Sudheer / Lewis, Leslie / Rao, Pragna

Bioanalysis

2019 Volume 12, Issue 2, Page(s) 111–124

Abstract: Aim: ...

Abstract	Aim:
MeSH term(s)	Biomarkers/metabolism ; Chromatography, High Pressure Liquid ; Chromatography, Liquid/methods ; Dried Blood Spot Testing/methods ; Humans ; Mass Spectrometry/methods ; Seizures/diagnosis ; Seizures/drug therapy ; Vitamins/pharmacology ; Vitamins/therapeutic use
Chemical Substances	Biomarkers ; Vitamins
Language	English
Publishing date	2019-12-19
Publishing country	England
Document type	Journal Article
ISSN	1757-6199
ISSN (online)	1757-6199
DOI	10.4155/bio-2019-0121
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Article: Treatment of

Gupta, Ashutosh / Shetty, Shiran / Mutalik, Srinivas / Chandrashekar H, Raghu / K, Nandakumar / Mathew, Elizabeth Mary / Jha, Abhishek / Mishra, Brahmeshwar / Rajpurohit, Siddheesh / Ravi, Gundawar / Saha, Moumita / Moorkoth, Sudheer

Heliyon

2023 Volume 9, Issue 10, Page(s) e20406

Abstract: Peptic ulcer disease (PUD) is one of the most prevalent gastro intestinal disorder which often leads to painful sores in the stomach lining and intestinal bleeding. ... ...

Abstract	Peptic ulcer disease (PUD) is one of the most prevalent gastro intestinal disorder which often leads to painful sores in the stomach lining and intestinal bleeding. Untreated
Language	English
Publishing date	2023-09-24
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e20406
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