title: New Fe(iii) and Co(ii) salen complexes with pendant distamycins: selective targeting of cancer cells by DNA damage and mitochondrial pathways.
abstract: Minor groove binding distamycin like moieties were conjugated with core salens and the corresponding Fe(iii) and Co(ii) complexes were synthesized. Herein, we have shown efficient DNA minor groove binding specificities along with excellent DNA cleavage capacities with metallosalen conjugates. The metal complexes showed toxicity toward various cancer cells over normal cells with high specificity. Interestingly, the Co(ii) complexes exhibited greater activity than the Fe(iii) complexes in accordance with the stronger affinity of the former in the biophysical studies. Active DNA damage, and prominent nuclear condensation along with the release of cytochrome-c from the mitochondria unanimously showed that the metal complexes followed apoptotic pathways to induce cell death.
authors.affiliation: Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India.
authors.forename: Asfa
authors.initials: A
authors.lastname: Ali
authors.affiliation: Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India.
authors.forename: Mohini
authors.initials: M
authors.lastname: Kamra
authors.affiliation: Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, USA.
authors.forename: Arunoday
authors.initials: A
authors.lastname: Bhan
authors.affiliation: Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, USA.
authors.forename: Subhrangsu S
authors.initials: SS
authors.lastname: Mandal
authors.affiliation: Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India and Indian Association for the Cultivation of Science, Kolkata, West Bengal 700 032, India. sb@orgchem.iisc.ernet.in.
authors.forename: Santanu
authors.initials: S
authors.lastname: Bhattacharya
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects*; D053837:DNA Cleavage; D004249:DNA Damage; D004214:Distamycins / Q000494:pharmacology*; D005029:Ethylenediamines / Q000494:pharmacology; D005290:Ferric Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002614:Chelating Agents; D056831:Coordination Complexes; D004214:Distamycins; D005029:Ethylenediamines; D005290:Ferric Compounds; D003035:Cobalt; D004247:DNA; C011452:disalicylaldehyde ethylenediamine