Multiple Functions of Generic Drugs: Future Perspectives of Aureolic Acid Group of Anti-Cancer Antibiotics and Non-Steroidal Anti-Inflammatory Drugs

Chakraborty, Hirak; Devi, Pukhrambam Grihanjali; Sarkar, Munna; Dasgupta, Dipak

doi:10.2174/138955708783955944

Cited by 19 publications

(16 citation statements)

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“…[1,2]. Some of these NSAIDs also have interesting spectroscopic properties that are sensitive to their microenvironment and can be used effectively as reporter of their interaction with biomolecules [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

A traditional painkiller as a probe for microheterogeneity in 1-propanol–water mixtures

Chakraborty

Sehanobish

Sarkar

2010

Chemical Physics Letters

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Section: Introductionmentioning

confidence: 99%

A traditional painkiller as a probe for microheterogeneity in 1-propanol–water mixtures

Chakraborty

Sehanobish

Sarkar

2010

Chemical Physics Letters

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“…Second, copper chelating drugs are gaining importance as a possible treatment for such diseases (Daniel et al 2004;Di Vaira et al 2004). Third, there has been a recent spate of studies to probe alternative therapeutic potential of the structurally related generic drug, Mithramycin (Chakraborty et al 2008). Studies show that these aureolic acid antibiotics can cross the blood-brain barrier, which makes them more important (Ferrante et al 2004).…”

Section: Discussionmentioning

confidence: 99%

“…K d is estimated from each data point (using Eq. 8) (Chakraborty et al 2008) show that CHR binds to Cu 2? with a relatively high affinity.…”

Section: Stoichiometry Of the (Chr): Cu 2? Complexmentioning

confidence: 99%

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Association of aureolic acid antibiotic, chromomycin A3 with Cu2+ and its negative effect upon DNA binding property of the antibiotic

et al. 2011

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Here we have examined the association of an aureolic acid antibiotic, chromomycin A3 (CHR), with Cu(2+). CHR forms a high affinity 2:1 (CHR:Cu(2+)) complex with dissociation constant of 0.08 × 10(-10) M(2) at 25°C, pH 8.0. The affinity of CHR for Cu(2+) is higher than those for Mg(2+) and Zn(2+) reported earlier from our laboratory. CHR binds preferentially to Cu(2+) in presence of equimolar amount of Zn(2+). Complex formation between CHR and Cu(2+) is an entropy driven endothermic process. Difference between calorimetric and van't Hoff enthalpies indicate the presence of multiple equilibria, supported from biphasic nature of the kinetics of association. Circular dichroism spectroscopy show that [(CHR)(2):Cu(2+)] complex assumes a structure different from either of the Mg(2+) and Zn(2+) complex reported earlier. Both [(CHR)(2):Mg(2+)] and [(CHR)(2):Zn(2+)] complexes are known to bind DNA. In contrast, [(CHR)(2):Cu(2+)] complex does not interact with double helical DNA, verified by means of Isothermal Titration Calorimetry of its association with calf thymus DNA and the double stranded decamer (5'-CCGGCGCCGG-3'). In order to interact with double helical DNA, the (antibiotic)(2) : metal (Mg(2+) and Zn(2+)) complexes require a isohelical conformation. Nuclear Magnetic Resonance spectroscopy shows that the Cu(2+) complex adopts a distorted octahedral structure, which cannot assume the required conformation to bind to the DNA. This report demonstrates the negative effect of a bivalent metal upon the DNA binding property of CHR, which otherwise binds to DNA in presence of metals like Mg(2+) and Zn(2+). The results also indicate that CHR has a potential for chelation therapy in Cu(2+) accumulation diseases. However cytotoxicity of the antibiotic might restrict the use.

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“…Second, with respect to the toxicity of MTH, two considerations should be made: (a) MTH analogs exhibiting safer pharmacological features and improved therapeutic index have been recently developed 55,58 and (b) novel transgenic mouse systems are available to study the effects in vivo of either free MTH and PM-MTH formulations. 59,60 For instance, the recently humanized transgenic mice carrying the entire human β-globin locus are very appealing for testing possible HbF inducers, since this experimental model does not suffer by the fact that an HbF-like hemoglobin is not produced by normal mice. 9 A further consideration is related to possible applications of PM-MTH to other pathologies including neoplastic diseases.…”

Section: Effect Of Pm-mth On Erpcsmentioning

confidence: 99%

Mithramycin encapsulated in polymeric micelles by microfluidic technology as novel therapeutic protocol for beta-thalassemia

Capretto

Mazzitelli

Brognara³

et al. 2012

IJN

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This report shows that the DNA-binding drug, mithramycin, can be efficiently encapsulated in polymeric micelles (PM-MTH), based on Pluronic ® block copolymers, by a new microfluidic approach. The effect of different production parameters has been investigated for their effect on PM-MTH characteristics. The compared analysis of PM-MTH produced by microfluidic and conventional bulk mixing procedures revealed that microfluidics provides a useful platform for the production of PM-MTH with improved controllability, reproducibility, smaller size, and polydispersity. Finally, an investigation of the effects of PM-MTH, produced by microfluidic and conventional bulk mixing procedures, on the erythroid differentiation of both human erythroleukemia and human erythroid precursor cells is reported. It is demonstrated that PM-MTH exhibited a slightly lower toxicity and more pronounced differentiative activity when compared to the free drug. In addition, PM-MTH were able to upregulate preferentially γ-globin messenger ribonucleic acid production and to increase fetal hemoglobin (HbF) accumulation, the percentage of HbF-containing cells, and their HbF content without stimulating α-globin gene expression, which is responsible for the clinical symptoms of β-thalassemia. These results represent an important first step toward a potential clinical application, since an increase in HbF could alleviate the symptoms underlying β-thalassemia and sickle cell anemia. In conclusion, this report suggests that PM-MTH produced by microfluidic approach warrants further evaluation as a potential therapeutic protocol for β-thalassemia.

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Multiple Functions of Generic Drugs: Future Perspectives of Aureolic Acid Group of Anti-Cancer Antibiotics and Non-Steroidal Anti-Inflammatory Drugs

Cited by 19 publications

References 1 publication

A traditional painkiller as a probe for microheterogeneity in 1-propanol–water mixtures

A traditional painkiller as a probe for microheterogeneity in 1-propanol–water mixtures

Association of aureolic acid antibiotic, chromomycin A3 with Cu2+ and its negative effect upon DNA binding property of the antibiotic

Mithramycin encapsulated in polymeric micelles by microfluidic technology as novel therapeutic protocol for beta-thalassemia

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