Computer assisted drug repurposing: Anti TB activity in non antibiotics
IR@NISCAIR: CSIR-NISCAIR, New Delhi - ONLINE PERIODICALS REPOSITORY (NOPR)
View Archive Info| Field | Value | |
| Title |
Computer assisted drug repurposing: Anti TB activity in non antibiotics
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| Creator |
Sangeeta, G P V
Nagasree, K Purna Jamullamudi, Risy Namratha Muthyala, Murali Krishna Kumar |
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| Subject |
Shape based virtual screening
Tanimoto combo score MABA assay MTT assay Axenic assay |
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| Description |
1295-1303
TB drug development is a formidable challenge at all times. As a part of our anti TB drug development program, we recently identified sertraline as a potential anti TB agent with an MIC-1.6µg/mL against MtbH37Rv. Sertraline is a popular marketed anti-depressant drug, hence we have planned to use the pharmacophoric signature of sertraline for virtual screening of drug database.We have performed shape based virtual screening of Drug Bank 5.0 database using vROCS software. Twenty chemically diverse drug molecules have been selected using Tanimoto COMBO score (TC>1.0). This gives chlormidazole, an obsolete anti-fungal drug as a Hit molecule with TC=1.67 (ranked 6<sup>th</sup>) and shows excellent anti TB activity (MIC 1.6µg/mL). It has been subjected to lead optimization studies and various chlormidazole analogues have been synthesized (<strong>1b-9b</strong>). They have been further screened for <em>in vitro </em>anti TB activity studies. Our results have successfully identified chlormidazole (<strong>5b</strong>) with MIC=1.6 µg/mL which can be repurposed as anti TB drug. Compounds <strong>1b</strong> and <strong>4b</strong> show selective potent anti TB activity. The compound <strong>8b</strong> shows selective antibacterial activity against <em>Staphylococcus aureus</em> (gram+ve) bacteria. Compounds <strong>2b</strong>, <strong>3b</strong>, <strong>5b</strong> and <strong>6b</strong> show potent anti TB activity along with antifungal activity against <em>Aspergillus niger</em>. In conclusion, our study has successfully identified potent anti-TB activity in Chlormidazole and its analogues. |
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| Date |
2018-10-11T10:40:33Z
2018-10-11T10:40:33Z 2018-10 |
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| Type |
Article
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| Identifier |
0975-0983(Online); 0376-4699(Print)
http://nopr.niscair.res.in/handle/123456789/45178 |
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| Language |
en_US
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| Rights |
<img src='http://nopr.niscair.res.in/image/cc-license-sml.png'> <a href='http://creativecommons.org/licenses/by-nc-nd/2.5/in' target='_blank'>CC Attribution-Noncommercial-No Derivative Works 2.5 India</a>
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| Publisher |
NISCAIR-CSIR, India
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| Source |
IJC-B Vol.57B(10) [October 2018]
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