Synthesis and Bio‐evaluation of GR135486X Derivatives as Potent Anti‐Tubercular Agents
Abstract The anilinopyridine derivatives were designed, synthesized and evaluated against Mycobacterium tuberculosis H37Rv. The detail SAR study was carried out using various analogues including positional isomers. The screening data revealed that the free −NH2 on pyridine ring is crucial for antitubercular activity. The current study identified three promising leads16 e,16 i and16 o with MIC 3.1, 3.1 and 1.2 μM, respectively. Important to note that the compound16 o showed excellent selectivity index of 135.58 when its antitubercular activity was compared with the inhibition of CHO−K1 cells. The other notable compounds were16 b,16 d,16 e,16 f,16 g,16 h,16 i,16 l and16 q which exhibited anti‐TB activity with MIC ≤25 μM. Interestingly, compounds16 e,16 i and16 o did not show inhibition of bacterial pathogen panel indicating the selectivity of this class of compounds towards Mtb. Furthermore, physico‐chemical and ADMET properties of the synthesized derivatives were studied. The compounds fulfill the criteria of Lipinski's rule of five for drug‐likeness..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
ChemistrySelect - 8(2023), 1 |
| Beteiligte Personen: |
Sangu, Komal G. [VerfasserIn] |
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| Anmerkungen: |
© 2023 Wiley‐VCH GmbH |
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| Umfang: |
17 |
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| doi: |
10.1002/slct.202204186 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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WLY016748557 |
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| 520 | |a Abstract The anilinopyridine derivatives were designed, synthesized and evaluated against Mycobacterium tuberculosis H37Rv. The detail SAR study was carried out using various analogues including positional isomers. The screening data revealed that the free −NH2 on pyridine ring is crucial for antitubercular activity. The current study identified three promising leads16 e,16 i and16 o with MIC 3.1, 3.1 and 1.2 μM, respectively. Important to note that the compound16 o showed excellent selectivity index of 135.58 when its antitubercular activity was compared with the inhibition of CHO−K1 cells. The other notable compounds were16 b,16 d,16 e,16 f,16 g,16 h,16 i,16 l and16 q which exhibited anti‐TB activity with MIC ≤25 μM. Interestingly, compounds16 e,16 i and16 o did not show inhibition of bacterial pathogen panel indicating the selectivity of this class of compounds towards Mtb. Furthermore, physico‐chemical and ADMET properties of the synthesized derivatives were studied. The compounds fulfill the criteria of Lipinski's rule of five for drug‐likeness. | ||
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