The thiosemicarbazone derivative of anthracene (ATSC, anthracene thiosemicarbazone 1) and its copper(II) complex (CuATSC, 2) were synthesized and characterized by spectroscopic, electrochemical, and crystallographic techniques. Interaction of 1 and 2 with calf thymus (CT) DNA was explored using absorption and emission spectral methods, and viscosity measurements reveal a partial-intercalation binding mode. Their protein binding ability was monitored by the quenching of tryptophan emission using bovine serum albumin (BSA) as a model protein. Furthermore, their cellular uptake, in vitro cytotoxicity testing on the HeLa cell line, and flow cytometric analysis were carried out to ascertain the mode of cell death. Cell cycle analysis indicated that 1 and 2 cause cell cycle arrest in sub-G1 phase.

A series of Ru(II) arene complexes of mono- and bidentate N-donor ligands with carboxyl or ester groups and chlorido ancillary ligands were synthesised and structurally characterised. The complexes have a distorted tetrahedral piano-stool geometry. The binding interaction was studied with calf thymus DNA (CT-DNA) by absorption titration, viscosity measurement, thermal melting, circular dichroism, ethidium bromide displacement assay and DNA cleavage of plasmid DNA (pBR322), investigated by gel electrophoresis. The dichlorido complexes bind covalently to DNA in the dark, similar to cisplatin, while the monochlorido complexes bind covalently on irradiation, similar to cisplatin analogues. The compounds are selectively cytotoxic against several tumour cell lines and show specific nonlinear correlation between dose and activity. This phenomenon is closely related to their potential to act preferentially as inhibitors of cell division.

Mixed-ligand Cu(ii) complexes of the type [Cu(doxycycline)(L)(H2O)2](NO3)2, where doxycycline = [4-(dimethylamino)-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide] and L = 2,2'-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 3) and dipyrido[3,2-a:2',3'-c]phenazine (dppz, 4) have been synthesised and characterised by structural, analytical, and spectral methods. The single-crystal X-ray structures of 1 and 2 exhibited two different geometries, distorted square-pyramidal and octahedral respectively as well as different coordination modes of doxycycline. Complexes 2-4 exhibit prominent plasmid DNA cleavage at significantly low concentrations probably by an oxidative mechanism. Matrix Metalloproteinase (MMP-2) inhibition studies revealed that all complexes inhibit MMP-2 similar to doxycycline which is a well-known MMP inhibitor with 3 being the most potent. IC50 values of doxycycline and 1-4 against MCF-7 (human breast cancer) and HeLa cell lines were almost equal in which 3 showed the highest efficiency (IC50 = 0.46 ± 0.05 μM), being consistent with its increased MMP inhibition potency. The antimalarial activities of these complexes against the chloroquine-sensitive Plasmodium falciparum NF54 and chloroquine-resistant Plasmodium falciparum Dd2 strains reveal that complex 3 exhibited a higher activity than artesunate drug against the chloroquine-resistant Dd2 strain.

The 2-anthryl benzimidazole derivatives (5-7) with hydrogen, carboxyl and benzoyl substituents at 5 th -position have been synthesized using silica supported periodic acid catalyst. DNA cleavage activity of 5-7 studied in presence of light using pBR322 plasmid DNA showed that cleavage activity varies with substitution at 5 th -position of benzimidazole derivatives. DNA binding studies using ethidium bromide displacement assay demonstrated non-intercalative binding mode of 5-7. Anticancer activity of these target molecules were tested against MCF-7 2 and HL-60 cell lines and exhibited remarkable activity in micromolar range. Cellular uptake and morphological changes were confirmed by fluorescence and confocal microscopy. Molecular docking study was carried out to explore the DNA binding mechanism with 5-7.Comparison of these values with that of cisplatin (IC 50 :40.45±0.29 µM for MCF-7 and 41.08±0.32 µM for HL-60) indicated that all these compounds (5-7) are more potent than cisplatin under the present experimental condition. Fig. 9 IC 50 in µM for 5-7 with MCF7 and HL60 cell line.Cellular morphology after treatment with 6 and 7 was observed using fluorescence and confocal microscopy. As can be seen from Fig. 10, the total fluorescence intensity throughout the cell is quite high. After 48 h, fluorescence was found in the cytosol, mostly concentrated in the area close to the nucleus. No fluorescence was detected in the nucleus indicating that only a fraction of the compound binds with nuclear DNA which was supported by DNA binding studies using ethidium bromide displacement assay. The cells treated with 5 seem to be healthy with more localized fluorescence whereas 7 gives diffused fluorescence. Further, cells treated with 6 seem to form uniform granule like structures evenly distributed throughout cytoplasm with distinct morphological changes indicative of cell death, demonstrating the better potency by 6.

A fluorescent Cu(ii) pyrenethiosemicarbazone complex exhibits enhanced DNA-cleavage and cytotoxicity on photoexcitation.