An ab initio study of model triazene-based anticancer agents

Doucet, Katherine G.; Glister, Julie F.; Pye, Cory C.

doi:10.1139/v10-023

Cited by 4 publications

(2 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The MTICs produced from path-1 and path-2 are tautomeric forms, whereas the water-mediated energy barrier for this 1,3-hydrogen shi is 5.93 kcal mol À1 . 36 The energy diagram for both pathways reveals that in spite of the lower TS-I for path-1, the TS-II and obtained products are more energy favoured for the second path. It appears that TMZ would prevail over ring opening in the more energy favoured path-1 that forms the rst MTIC tautomer but then undergoes tautomerism to generate the next MTIC tautomer (Scheme 1), which decomposes through the second path.…”

Section: Hydrolytic Degradation Mechanism Of Tmz To Mticmentioning

confidence: 95%

Mechanistic study of the hydrolytic degradation and protonation of temozolomide

Mirzaei

Khalilian

2015

RSC Adv.

View full text Add to dashboard Cite

show abstract

Section: Hydrolytic Degradation Mechanism Of Tmz To Mticmentioning

confidence: 95%

Mechanistic study of the hydrolytic degradation and protonation of temozolomide

Mirzaei

Khalilian

2015

RSC Adv.

View full text Add to dashboard Cite

show abstract

“…The addition of the LUVs decreased the absorbance of TMZ very slightly and gradually, while maintaining the shape of the spectrum, which discards drug degradation and suggests some interaction between the drug and the lipid membrane. The small decrease in absorbance could be explained by the existence in solution of two stable rotamers of TMZ [59]. Recently, Khallilian et al reported that the rotation of carboxamide moiety in TMZ leads to two rotamers with slight differences in their extinction coefficients and dipole moments; Rotamer 1 being more stable than Rotamer 2 [60].…”

Section: Interaction Of Tmz With Model Membranesmentioning

confidence: 99%

The Interaction of Temozolomide with Blood Components Suggests the Potential Use of Human Serum Albumin as a Biomimetic Carrier for the Drug

et al. 2020

View full text Add to dashboard Cite

The interaction of temozolomide (TMZ) (the main chemotherapeutic agent for brain tumors) with blood components has not been studied at the molecular level to date, even though such information is essential in the design of dosage forms for optimal therapy. This work explores the binding of TMZ to human serum albumin (HSA) and alpha-1-acid glycoprotein (AGP), as well as to blood cell-mimicking membrane systems. Absorption and fluorescence experiments with model membranes indicate that TMZ does not penetrate into the lipid bilayer, but binds to the membrane surface with very low affinity. Fluorescence experiments performed with the plasma proteins suggest that in human plasma, most of the bound TMZ is attached to HSA rather than to AGP. This interaction is moderate and likely mediated by hydrogen-bonding and hydrophobic forces, which increase the hydrolytic stability of the drug. These experiments are supported by docking and molecular dynamics simulations, which reveal that TMZ is mainly inserted in the subdomain IIA of HSA, establishing π-stacking interactions with the tryptophan residue. Considering the overexpression of albumin receptors in tumor cells, our results propose that part of the administered TMZ may reach its target bound to plasma albumin and suggest that HSA-based nanocarriers are suitable candidates for designing biomimetic delivery systems that selectively transport TMZ to tumor cells.

show abstract

The simulation of UV spectroscopy and electronic analysis of temozolomide and dacarbazine chemical decomposition to their metabolites

Khalilian

Mirzaei

2016

J Mol Model

View full text Add to dashboard Cite

The electronic features of anti-tumor agent, temozolomide, and its degradation products (MTIC and metabolite AIC) have been traced by means of UV absorption spectroscopy in vacuo and aqueous media. For comparison, electronic spectra of related structures and drugs (e.g., dacarbazine) were also investigated. These investigations were carried out using time-dependent density functional theory (TD-DFT) method while the conductor like screening model (COSMO) were applied for the inclusion of solvent effects in electronic spectra. From functional benchmarking, two methods; B3LYP and O3LYP were selected among several other methods with 6-311+G(2d,p) basis set aiming to get the best results in accord with the experimental values. An assessment of the obtained spectra has shown that O3LYP functional gives a mean absolute error (MAE) from experimental absorption peaks of 4.3 nm compared to the 7.2 nm MAE value at B3LYP level in aqueous media. Furthermore, since the structural and tautomeric conformers affect the electronic spectra, conformational preferences have been analyzed in temozolomide, dacarbazine, and their related structures. Temozolomide structure possesses two rotamers that differ in the orientation of carboxamide moiety with a small energy difference (energy difference of 1.39 kcal mol in vacuo and 0.35 kcal mol in aqueous media at B3LYP/6-311++G(2df,3pd). The more stable and meta-stable TMZ rotamer have shown their absorption maxima at 329-334 nm, respectively, at O3LYP level in aqueous media. Applying statistical calculation according to Boltzmann population formula at 25 °C and computed weighed mean estimates the λ of temozolomide at 331 nm, which is in notable agreement with the experimental value (330 nm). Moreover, molecular orbital composition analysis has been conducted in order to interpret these findings. Graphical Abstract Temozolomide and dacarbazine.

show abstract

An ab initio study of model triazene-based anticancer agents

Cited by 4 publications

References 11 publications

Mechanistic study of the hydrolytic degradation and protonation of temozolomide

Mechanistic study of the hydrolytic degradation and protonation of temozolomide

The Interaction of Temozolomide with Blood Components Suggests the Potential Use of Human Serum Albumin as a Biomimetic Carrier for the Drug

The simulation of UV spectroscopy and electronic analysis of temozolomide and dacarbazine chemical decomposition to their metabolites

Contact Info

Product

Resources

About