The DNA mismatch repair (MMR) system is involved in the correction of base/base mismatches and insertion/deletion loops arising during replication. In addition, some of the MMR components participate in recombination and double-strand break repair as well as cell cycle regulation and apoptosis. The inactivation of MMR genes, usually hMSH2 or hMLH1, is associated with human colorectal cancers an...

The discovery of DNA topoisomerases has added a new dimension to the study of anticancer drugs. In the last years detailed investigation of bi- and ter-benzimidazole derivatives revealed that these compounds are a new class of topoisomerase I inhibitors that poisons mammalian topoisomerase I. In this context a survey about topoisomerase I poisoning activity and cytotoxicity of bi- and ter-benzi...

A human Burkitt lymphoma cell line, Raji-HN2, made 10-fold more resistant to nitrogen mustard (HN2) than the parental Raji cell line, exhibited the following characteristics when compared to the parental Raji cells: (i) decreased HN2-induced DNA interstrand crosslinking; (ii) increased (3-fold) DNA topoisomerase II [DNA topoisomerase (ATP-hydrolyzing), EC 5.99.1.3] activity; (iii) increased (4-...

Natural products have been widely used in traditional medicines and are a valuable source for new drug discovery. On the other hand, extensive molecular modeling based on crystallographic data was used to aid the design of synthetic analogues of the natural products. Therefore, in this study, we have proposed the use of molecular modeling and docking techniques to design some potential active a...

Two set of 2-aryl-5,6-dihydropyrrolo[2,1-a] isoquinolines were designed and synthesized to evaluate their biological activities as topoisomerase inhibitors. Cytotoxic activity of the synthesized compounds 4a-e and 7a-d was assessed against several human cancer cell lines, including MCF-7 (breast cancer cell), HepG2 (liver hepatocellular cells), A549 (adenocarcinomic human alveolar basal epithel...

Objective: The present study discusses molecular docking of some novel coumarin–benzothiazole Schiff bases and the prediction pharmacokinetic properties potent molecules by computational method. Methods: Five protein targets were selected for their structures taken from RCSB Protein Data Bank in PDB format. Preparation proteins was done using Discovery Studio 2021 Client. A total twenty derivat...

The genome is organized into large scale structures in the interphase nucleus. Pericentromeric heterochromatin represents one such compartment characterized by histones H3 and H4 tri-methylated at K9 and K20 respectively and with a correspondingly low level of histone acetylation. HP1 proteins are concentrated in pericentric heterochromatin and histone deacetylase inhibitors such as trichostati...

Most DNA intercalators and epipodophyllotoxins inhibit mammalian topoisomerase II by trapping the enzyme within DNA cleavage complexes that can be detected in cells as protein-associated DNA strand breaks. We have characterized previously a line of Chinese hamster cells (DC3F/9-OHE cells) the resistance of which to the cytotoxic effect of intercalators and etoposide is associated with a reduced...

The two DNA intercalators, actinomycin D and 2-methyl-9-hydroxy-ellipticine, and the DNA minor groove ligant DAPI inhibited the growth of the haloarchaeon Halobacterium sp. GRB and bind to its plasmid pGRB-1. In contrast to specific DNA topoisomerase II inhibitors, they produced neither double-stranded breaks nor relaxation of plasmidic DNA. The two DNA intercalators inhibited positive supercoi...

Poly(ADP-ribose) polymerase-1 (PARP-1) is known to have an important role in camptothecin sensitivity and interacts with topoisomerase I. In the present study, the impact of PARP-1 on the topoisomerase I-DNA complex stabilized by camptothecin was assessed. It was shown that NH2 terminus-truncated topoisomerase I (amino acids 201-765) showed at least 4-fold less sensitivity to camptothecin than ...