Potential antitumor agents. 10. Synthesis and biochemical properties of 5-N-alkylamino-, N,N-dialkylamino-, and N-alkylacetamido-1-formylisoquinoline thiosemicarbazones

Mooney, Paul D.; Booth, Barbara A.; Moore, E. Colleen; Agrawal, Krishna C.; Sartorelli, Alan C.

doi:10.1021/jm00257a004

Cited by 24 publications

(8 citation statements)

References 2 publications

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“…The first set includes derivatives of 5-substituted-2-formylpyridine thiosemicarbazones and the second set includes derivatives of 4'-substituted-5-hydroxy-2-formylpyridine thiosemicarbazone 33 . The derivatives of both the sets are included in Table 1 and 2 respectively.1-Formylisoquinoline thiosemicarbazone derivatives 34,35 have also been divided into two different sets on the basis of the measurement of their biological activity and are presented in Table 3 (biological activity has been measured in terms of K 50 ) and Table 4 (biological activity in terms of I 50 ). Thus the QSAR study of all the four sets has been discussed as below.…”

Section: Resultsmentioning

confidence: 99%

[Retracted] DFT Based QSAR Study of Enzyme Ribonucleoside Diphosphate Reductase

Ansari¹,

Khan²,

Khan³

2009

Journal of Chemistry

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Quantum chemical descriptors such as heat of formation, energy of HOMO, total energy, absolute hardness and chemical potential in different combinations have been used to develop QSAR models of inhibitors of enzyme ribonucleoside diphosphate reductase, RDR. The inhibitors are mainly derivatives of 1-formylisoquinoline thiosemicarbazone and 2-formylpyridine thiosemicarbazone. The values of various descriptors have been evaluated with the help of Win MOPAC 7.21 software using DFT method. Multiple linear regression analysis has been made with the help of above mentioned descriptors using the same software. Regression equations have been found to be successful models as indicated by the regression coefficientr2having the value as high as 0.96 and cross validation coefficientrCV2having the value approaching 0.95. The value of these two coefficients is indicative of high order of reliability for the proposed prediction. The results obtained are also validated on account of the closeness of observed and predicted inhibitory activities. The best combination of descriptors is heat of formation, total energy and energy of HOMO. Thus the prediction of suitability of inhibitors of the enzyme RDR can be made with the help of the best regression equation.

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Section: Resultsmentioning

confidence: 99%

[Retracted] DFT Based QSAR Study of Enzyme Ribonucleoside Diphosphate Reductase

Ansari¹,

Khan²,

Khan³

2009

Journal of Chemistry

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“…NMR spectra were run on all compounds and are in agreement with assigned structures. Deuterated chloroform (3)(4)(5)(6)(7)(8)(9)(10)(11)(13)(14)(15), deuterated dimethyl sulfoxide (2 and 12), and deuterium oxide (1) were the solvents with tetramethylsilane as the internal or external reference. Chromatographic separations were achieved by means of a Waters Associates Model ALC-201 with 6000 solvent delivery system.…”

Section: Methodsmentioning

confidence: 99%

Phosphorus-nitrogen compounds. 20. Thiophosphorus hydrazones

Cates¹,

Cho²,

Smith³

et al. 1976

J. Med. Chem.

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Six pyridine-2-carboxaldehyde, one pyridine N-oxide 2-carboxaldehyde, and five diketone thiophosphoric hydrazones, three thiophosphoric hydrazides, and two cupric chelates were synthesized. The chelates and nine of the hydrazones were tested against Ehrlich ascites carcinoma. Seven of these latter agents were administered concurrently with either cupric and/or ferrous salts to mice bearing this tumor. The greatest activity was found with the chelate, cimethyl pyridine-2-carboxyaldehyde phosphorothioic hydrazone-copper (1:1). The hydrazone portion of this chelate also formed a ligand-copper (2:1) complex. Although all of the hydrazones but one were inactive when evaluated alone, the concurrent injection of cupric ion increased survival times by an avoli alkaline phosphatase was found to be inhibited by two thiosemicarbazones in a manner similar to that previously reported by these agents against alkaline phosphatase derived from Sarcoma 180-6-thiopurine resistant ascites cells. None of the 14 hydrazides or hydrazones tested against E. coli enzyme displayed significant inhibition.

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“…A series of non-methylated 4' primary amine compounds was first synthesized, with known compounds HCT-1, HCT-4, and HCT-5 included to gauge whether fluorination of the isoquinoline proved beneficial for biological activity. 41,42 Within the 4' primary amine series, fluorination at the isoquinoline 4-position (HCT-2) did not show an increase in potency relative to unsubstituted analog HCT-1. However, fluorination at the 6-position (HCT-3) showed a 3fold increase in potency, demonstrating that the fluorine position impacts the potency of these compounds.…”

Section: Table 1 Substitution Patterns Of Hcts 1-15mentioning

confidence: 99%

Evaluation of Potent Isoquinoline-Based Thiosemicarbazone Antiproliferatives Against Solid Tumor Models

D¹,

Poddar²,

Pan

et al. 2019

Preprint

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The lead compound, an ⍺-N-heterocyclic carboxaldehyde thiosemicarbazone HCT-13, was highly potent against a panel of pancreatic, small cell lung carcinoma, and prostate cancer models, with IC90 values in the low-to-mid nanomolar range. We show that the cytotoxicity of HCT-13 is copper-dependent, that it acts as a copper ionophore, induces production of reactive oxygen species (ROS), and promotes mitochondrial dysfunction and S-phase arrest. Lastly, DNA damage response/replication stress response (DDR/RSR) pathways, specifically Ataxia-Telangiectasia Mutated (ATM) and Rad3-related protein kinase (ATR), were identified as actionable adaptive resistance mechanisms following HCT-13 treatment. Taken together, HCT-13 is potent against solid tumor models and warrants in vivo evaluation against aggressive tumor models, either as a single agent or as part of a combination therapy.

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Potential antitumor agents. 10. Synthesis and biochemical properties of 5-N-alkylamino-, N,N-dialkylamino-, and N-alkylacetamido-1-formylisoquinoline thiosemicarbazones

Cited by 24 publications

References 2 publications

[Retracted] DFT Based QSAR Study of Enzyme Ribonucleoside Diphosphate Reductase

[Retracted] DFT Based QSAR Study of Enzyme Ribonucleoside Diphosphate Reductase

Phosphorus-nitrogen compounds. 20. Thiophosphorus hydrazones

Evaluation of Potent Isoquinoline-Based Thiosemicarbazone Antiproliferatives Against Solid Tumor Models

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