Molecular modeling and spectroscopic studies of semustine binding with DNA and its comparison with lomustine–DNA adduct formation

  title={Molecular modeling and spectroscopic studies of semustine binding with DNA and its comparison with lomustine–DNA adduct formation},
  author={Shweta Agarwal and Deepti Chadha and Ranjana Mehrotra},
  journal={Journal of Biomolecular Structure and Dynamics},
  pages={1653 - 1668}
Chloroethyl nitrosoureas constitute an important family of cancer chemotherapeutic agents, used in the treatment of various types of cancer. They exert antitumor activity by inducing DNA interstrand cross-links. Semustine, a chloroethyl nitrosourea, is a 4-methyl derivative of lomustine. There exist some interesting reports dealing with DNA-binding properties of chloroethyl nitrosoureas; however, underlying mechanism of cytotoxicity caused by semustine has not been precisely and completely… 

Deciphering molecular aspects of interaction between anticancer drug mitoxantrone and tRNA

Investigation into drug–tRNA interaction can play an essential role in the rational development of RNA targeting chemotherapeutic agents, which also delineate the structural–functional relationship between drug and its target at molecular level.

Investigation of Anti-Cancer Drug Nimustine Interaction with Calf Thymus DNA

The prediction and investigation of binding properties of nimustine with DNA using molecular modeling and UV–Visible spectroscopic technique may help in designing and synthesis of new chloroethyl nitrosourea derivatives with improved efficacy and specificity for the target molecules.

Structural, conformational and thermodynamic aspects of groove-directed-intercalation of flavopiridol into DNA

The conclusions drawn from this study could be helpful in unveiling mechanism of cytoxicity induced by flavopiridol that can be further applied in the development of flavonoid-based new chemotherapeutics with more specificity and better efficacy.

tRNA binding with anti-cancer alkaloids-nature of interaction and comparison with DNA-alkaloids adducts.

Multivariate spectrochemical analysis of interactions of three common Isatin derivatives to calf thymus DNA in vitro

The common soft/hard chemometric methods were used not only to resolve pure concentration and spectral profiles of components using the acquired spectra but also to calculate Stern–Volmer quenching constants, binding stoichiometry, apparent binding constants (Ka),binding constants (Kb), and thermodynamic parameters.

Biological applications of pyrazoline-based half-sandwich ruthenium(III) coordination compounds

A series of pyrazoline-based half-sandwich organometallic ruthenium complexes have been synthesized and well characterized with an aim to study their biological activity and to explore the trend in DNA-binding affinities of organometric ruthensium complexes and the important differences in some related properties.

Anticancer activity of pyrimidodiazepines based on 2-chloro-4-anilinoquinazoline: synthesis, DNA binding and molecular docking

CompARE analysis revealed that 16c may possess a mechanism of action through DNA binding that is similar to that of CCNU (lomustine), where 16c showed high cytotoxic activity, which was 10.0-fold higher than the standard anticancer agent adriamycin/doxorubicin against ten cancer cell lines.

Anticancer Drugs: Recent Strategies to Improve Stability Profile, Pharmacokinetic and Pharmacodynamic Properties

The latest advances in knowledge regarding the development of effective highly stable anticancer drugs formulated as stable prodrugs or entrapped in nanosystems are summarized.



A Structural Insight into Major Groove Directed Binding of Nitrosourea Derivative Nimustine with DNA: A Spectroscopic Study

Results of the present study demonstrate that nimustine is not a simple alkylating agent rather it causes major grove-directed-alkylation, which may contribute in the development of new nitrosourea therapeutics with better efficacy and fewer side effects.

FTIR and circular dichroism spectroscopic study of interaction of 5-fluorouracil with DNA.

Spectroscopic studies of the effects of anticancer drug mitoxantrone interaction with calf-thymus DNA.

Binding of an indole alkaloid, vinblastine to double stranded DNA: a spectroscopic insight in to nature and strength of interaction.

DNA interaction studies of an anticancer plant alkaloid, vincristine, using Fourier transform infrared spectroscopy.

Both intercalative and external binding modes are observed for vincristine binding with DNA, with an estimated binding constant K = 1.0 × 10(3) M(-1).

Agarose Gel Electrophoresis and Fluorometric Assays for the Determination of DNA Cross-Linking Induced by Semustine

It was found that the cross-links of DNA induced by drugs increased progressively with the reaction time, tending towards a maximum stable value at about 8h, which suggests that the formation of DNA interstrand cross- linking may undergo an induction period.

Mechanism of action of fotemustine, a new chloroethylnitrosourea anticancer agent: evidence for the formation of two DNA-reactive intermediates contributing to cytotoxicity.

It is proposed that FM breaks down to form a short-lived intermediate, 2-chloroethyldiazohydroxide, which rapidly generates O6-guanine lesions responsible for the drug's initial activity and a long lived iminol tautomerresponsible for the remaining O6 guanine alkylation and cytotoxicity.

Comparative Investigations of Deoxyribonucleic Acid Interstrand Crosslinks Induced by Semustine Using Fluorescence and High Performance Liquid Chromatography-Mass Spectrometry

Semustine(Me-CCNU) is an important alkylating agent used in the clinical treatment of cancer.The anticancer mechanism of Me-CCNU is associated with the formation of DNA interstrand

The structure of DNA within cationic lipid/DNA complexes.

An Overview of Analytical Techniques Employed to Evidence Drug-DNA Interactions. Applications to the Design of Genosensors

The present chapter describes analytical techniques used to achieve a deeper knowledge of the nature of the interactions and their application to the design of different devices consisting of short single stranded oligonucleotides produced in vitro by well-established methods that are capable to detect genetic peculiarities and diseases.