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Abstract

The nucleus of the cell serves to maintain, regulate, and replicate the critical genetic information encoded by the genome. Genomic DNA is highly associated with proteins that enable simple nuclear structures such as nucleosomes to form higher-order organisation such as chromatin fibres. The temporal association of regulatory proteins with DNA creates a dynamic environment capable of quickly responding to cellular requirements and distress. The response is often mediated through alterations in the chromatin structure, resulting in changed accessibility of specific DNA sequences that are then recognized by specific proteins. Anti-cancer drugs that target cellular DNA have been used clinically for over four decades, but it is only recently that nuclease specific drugs have been developed to not only target the DNA but also other components of the nuclear structure and its regulation. In this review, we discuss some of the new drugs aimed at primary DNA sequences, DNA secondary structures, and associated proteins, keeping in mind that these agents are not only important from a clinical perspective but also as tools for understanding the nuclear environment in normal and cancer cells.

A novel DNA intercalator, butylamino-pyrimido[4′,5′:4,5]selenolo(2,3-b)quinoline, induces cell cycle arrest and apoptosis in leukemic cells

“…It is possible that alkyl nature of the butylamino substitution helps the pyrimidoselenoloquinoline skeleton to have more retention time by burying We were interested to know which cellular processes in growing populations of leukemic cells (K562, Nalm6) could be affected by BPSQ. It is an established fact that many small molecules can inhibit cell growth in vitro through their cytotoxic effects [9,37,38]. Our studies using trypan blue and MTT assays indicated a significant reduction in number of metabolically active cells after treating with BPSQ.…”

Selective binding of small molecules to DNA: Application and perspectives

“…For example, the ligand/DNA interaction results in DNA structural distortion or damage that impedes replication or transcription by blocking the movement of helicases, topoisomerases and polymerases. Importantly, some compounds can selectively bind to abundant long adenine-thymine (AT) repeat sequences that are essential for normal chromosome metabolism, or guanosine-cytosine (GC) repeat sequences that are related to transcription of some apoptosis-suppressive gene [40][41].…”

Synthesis, Cytotoxic Evaluation, and In Silico Studies of 4‐Substituted Coumarins

“…It is one of the most vital health problems of the current era and is a leading cause of death [2]. Although, many efforts have been made to discover new agents endowed with cytotoxic actions, still these agents are suffering from serious limitations such as lack of selectivity and life-threatening side effects [3].…”