Density Functional Studies of Bis-alkylating Nitrogen Mustards
Pp. 121-186 (66)
Pradip Kr. Bhattacharyya, Sourab Sinha, Nabajit Sarmah and Bhabesh Chandra Deka
Nitrogen mustards are the most extensively used chemotherapeutic agent
since their evolution in the mid-1940s. The high degree of cytotoxicity of these drugs is
attributed to their ability to form DNA interstrand cross-linked adducts, thereby
inhibiting DNA replication. Interstrand cross-linking occurs via formation of an
unstable intermediate, the aziridinium ion and formation of mono-adducts. Mustine, the
first member of this family, suffers from some serious drawbacks such as high rate of
hydrolysis. Therefore its stable analogs have been sought; and since its discovery
hundreds of analogs have been synthesized.
This article presents a brief introduction to nitrogen mustards and deliberates on the
works already devoted to establishing the mechanism of action of this class of drug. A
brief discussion on DFT and DFRT is also furnished in section 1.2. Further,
computational studies performed on nitrogen mustards are discussed in section 1.3 and
1.4. Section 1.4 of the article consists of research works from our group and has special
reference to DFT and DFRT.
Anticancer drug, aziridinium ion, bis-alkylating agent, cancer
chemotherapy, chemical hardness, chemical potential, chlorambucil,
computational chemistry, density functional theory (DFT), density functional
reactivity theory (DFRT), DNA alkylation, external electric field, maximum
hardness principle, minimum electrophilicity principle, melphalan, Mustine,
nitrogen mustards, reactivity descriptors, steroid-linked nitrogen mustard,
Department of Chemistry, Arya Vidyapeeth College, Assam-781016, India.