Development of derivatives of 3, 3'-diindolylmethane as potent Leishmania donovani bi-subunit topoisomerase IB poisons.
BACKGROUND: The development of 3, 3'-diindolyl methane (DIM) resistant parasite Leishmania donovani (LdDR50) by adaptation with increasing concentrations of the drug generates random mutations in the large and small subunits of heterodimeric DNA topoisomerase I of Leishmania (LdTOP1LS). Mutatio...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3236199?pdf=render |
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| author | Amit Roy Sayan Chowdhury Souvik Sengupta Madhumita Mandal Parasuraman Jaisankar Ilda D'Annessa Alessandro Desideri Hemanta K Majumder |
| author_facet | Amit Roy Sayan Chowdhury Souvik Sengupta Madhumita Mandal Parasuraman Jaisankar Ilda D'Annessa Alessandro Desideri Hemanta K Majumder |
| author_sort | Amit Roy |
| collection | DOAJ |
| description | BACKGROUND: The development of 3, 3'-diindolyl methane (DIM) resistant parasite Leishmania donovani (LdDR50) by adaptation with increasing concentrations of the drug generates random mutations in the large and small subunits of heterodimeric DNA topoisomerase I of Leishmania (LdTOP1LS). Mutation of large subunit of LdTOP1LS at F270L is responsible for resistance to DIM up to 50 µM concentration. METHODOLOGY/PRINCIPAL FINDINGS: In search of compounds that inhibit the growth of the DIM resistant parasite and inhibit the catalytic activity of mutated topoisomerase I (F270L), we have prepared three derivatives of DIM namely DPDIM (2,2'-diphenyl 3,3'-diindolyl methane), DMDIM (2,2'-dimethyl 3,3'-diindolyl methane) and DMODIM (5,5'-dimethoxy 3,3'-diindolyl methane) from parent compound DIM. All the compounds inhibit the growth of DIM resistant parasites, induce DNA fragmentation and stabilize topo1-DNA cleavable complex with the wild type and mutant enzyme. CONCLUSION: The results suggest that the three derivatives of DIM can act as promising lead molecules for the generation of new anti-leishmanial agents. |
| first_indexed | 2024-12-14T00:39:52Z |
| format | Article |
| id | doaj.art-544a5a80c83547f6bfc1741c3835a257 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T00:39:52Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-544a5a80c83547f6bfc1741c3835a2572022-12-21T23:24:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01612e2849310.1371/journal.pone.0028493Development of derivatives of 3, 3'-diindolylmethane as potent Leishmania donovani bi-subunit topoisomerase IB poisons.Amit RoySayan ChowdhurySouvik SenguptaMadhumita MandalParasuraman JaisankarIlda D'AnnessaAlessandro DesideriHemanta K MajumderBACKGROUND: The development of 3, 3'-diindolyl methane (DIM) resistant parasite Leishmania donovani (LdDR50) by adaptation with increasing concentrations of the drug generates random mutations in the large and small subunits of heterodimeric DNA topoisomerase I of Leishmania (LdTOP1LS). Mutation of large subunit of LdTOP1LS at F270L is responsible for resistance to DIM up to 50 µM concentration. METHODOLOGY/PRINCIPAL FINDINGS: In search of compounds that inhibit the growth of the DIM resistant parasite and inhibit the catalytic activity of mutated topoisomerase I (F270L), we have prepared three derivatives of DIM namely DPDIM (2,2'-diphenyl 3,3'-diindolyl methane), DMDIM (2,2'-dimethyl 3,3'-diindolyl methane) and DMODIM (5,5'-dimethoxy 3,3'-diindolyl methane) from parent compound DIM. All the compounds inhibit the growth of DIM resistant parasites, induce DNA fragmentation and stabilize topo1-DNA cleavable complex with the wild type and mutant enzyme. CONCLUSION: The results suggest that the three derivatives of DIM can act as promising lead molecules for the generation of new anti-leishmanial agents.http://europepmc.org/articles/PMC3236199?pdf=render |
| spellingShingle | Amit Roy Sayan Chowdhury Souvik Sengupta Madhumita Mandal Parasuraman Jaisankar Ilda D'Annessa Alessandro Desideri Hemanta K Majumder Development of derivatives of 3, 3'-diindolylmethane as potent Leishmania donovani bi-subunit topoisomerase IB poisons. PLoS ONE |
| title | Development of derivatives of 3, 3'-diindolylmethane as potent Leishmania donovani bi-subunit topoisomerase IB poisons. |
| title_full | Development of derivatives of 3, 3'-diindolylmethane as potent Leishmania donovani bi-subunit topoisomerase IB poisons. |
| title_fullStr | Development of derivatives of 3, 3'-diindolylmethane as potent Leishmania donovani bi-subunit topoisomerase IB poisons. |
| title_full_unstemmed | Development of derivatives of 3, 3'-diindolylmethane as potent Leishmania donovani bi-subunit topoisomerase IB poisons. |
| title_short | Development of derivatives of 3, 3'-diindolylmethane as potent Leishmania donovani bi-subunit topoisomerase IB poisons. |
| title_sort | development of derivatives of 3 3 diindolylmethane as potent leishmania donovani bi subunit topoisomerase ib poisons |
| url | http://europepmc.org/articles/PMC3236199?pdf=render |
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