2c2t: Difference between revisions
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==Overview== | ==Overview== | ||
Two boron-containing, ortho-icosahedral carborane lipophilic antifolates, were synthesized, and the crystal structures of their ternary complexes, with human dihydrofolate reductase (DHFR) and dihydronicotinamide adenine, dinucleotide phosphate were determined. The compounds were screened for, activity against DHFR from six sources (human, rat liver, Pneumocystis, carinii, Toxoplasma gondii, Mycobacterium avium, and Lactobacillus casei), and showed good to modest activity against these enzymes. The compounds, were also tested for antibacterial activity against L. casei, M., tuberculosis H37Ra, and three M. avium strains and for cytotoxic activity, against seven different human tumor cell lines. Antibacterial and, cytotoxic activity was modest, with one sample, the closo-carborane 4, .. | Two boron-containing, ortho-icosahedral carborane lipophilic antifolates, were synthesized, and the crystal structures of their ternary complexes, with human dihydrofolate reductase (DHFR) and dihydronicotinamide adenine, dinucleotide phosphate were determined. The compounds were screened for, activity against DHFR from six sources (human, rat liver, Pneumocystis, carinii, Toxoplasma gondii, Mycobacterium avium, and Lactobacillus casei), and showed good to modest activity against these enzymes. The compounds, were also tested for antibacterial activity against L. casei, M., tuberculosis H37Ra, and three M. avium strains and for cytotoxic activity, against seven different human tumor cell lines. Antibacterial and, cytotoxic activity was modest, with one sample, the closo-carborane 4, showing about 10-fold greater activity. The less toxic nido-carborane 2, was also tested as a candidate for boron neutron capture therapy, but, showed poor tumor retention and low selectivity ratios for boron, distribution in tumor tissue versus normal tissue. | ||
==About this Structure== | ==About this Structure== | ||
2C2T is a | 2C2T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NDP, 39B, 39E and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2C2T OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: reductase]] | [[Category: reductase]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 12:47:11 2007'' | ||
