Molecular properties prediction and synthesis of novel 1,3,4-oxadiazole analogues as potent antimicrobial and antitubercular agents
Copyright © 2011 Elsevier Ltd. All rights reserved..
In the present investigation, a series of 1,5-dimethyl-2-phenyl-4-{[(5-aryl-1,3,4-oxadiazol-2-yl)methyl]amino}-1,2-dihydro-3H-pyrazol-3-one were subjected to molecular properties prediction, drug-likeness by Molinspiration (Molinspiration, 2008) and MolSoft (MolSoft, 2007) software, lipophilicity and solubility parameters using ALOGPS 2.1 program. The compounds followed the Lipinski 'Rule of five' were synthesized for antimicrobial and antitubercular screening as oral bioavailable drugs/leads. Maximum drug-likeness model score (0.95) was found for compound, 4a. All the synthesized compounds were characterized by IR, NMR and mass spectral analysis followed by antimicrobial and antimycobacterial screening. Among the title compounds, compound 4d showed pronounced activity against Mycobacterium tuberculosis H(37)Rv and isoniazid resistant M. tuberculosis (INHR-TB) with minimum inhibitory concentrations (MICs) 0.78μM and 1.52 μM, respectively. The compound, 4a showed maximum activity against all bacterial strains with MIC 4-8 μg/mL comparable to standard drug ciprofloxacin, while the compounds, 4e and 4k showed maximum antifungal activity with MIC 8-16 μg/mL less active than standard drug fluconazole.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2011 |
|---|---|
| Erschienen: |
2011 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
|---|---|
| Enthalten in: |
Bioorganic & medicinal chemistry letters - 21(2011), 24 vom: 15. Dez., Seite 7246-50 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Ahsan, Mohamed Jawed [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Anti-Infective Agents |
|---|
| Anmerkungen: |
Date Completed 12.03.2012 Date Revised 21.11.2011 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.bmcl.2011.10.057 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM212921673 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM212921673 | ||
| 003 | DE-627 | ||
| 005 | 20231224020524.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2011 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.bmcl.2011.10.057 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0710.xml |
| 035 | |a (DE-627)NLM212921673 | ||
| 035 | |a (NLM)22071303 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Ahsan, Mohamed Jawed |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Molecular properties prediction and synthesis of novel 1,3,4-oxadiazole analogues as potent antimicrobial and antitubercular agents |
| 264 | 1 | |c 2011 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 12.03.2012 | ||
| 500 | |a Date Revised 21.11.2011 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2011 Elsevier Ltd. All rights reserved. | ||
| 520 | |a In the present investigation, a series of 1,5-dimethyl-2-phenyl-4-{[(5-aryl-1,3,4-oxadiazol-2-yl)methyl]amino}-1,2-dihydro-3H-pyrazol-3-one were subjected to molecular properties prediction, drug-likeness by Molinspiration (Molinspiration, 2008) and MolSoft (MolSoft, 2007) software, lipophilicity and solubility parameters using ALOGPS 2.1 program. The compounds followed the Lipinski 'Rule of five' were synthesized for antimicrobial and antitubercular screening as oral bioavailable drugs/leads. Maximum drug-likeness model score (0.95) was found for compound, 4a. All the synthesized compounds were characterized by IR, NMR and mass spectral analysis followed by antimicrobial and antimycobacterial screening. Among the title compounds, compound 4d showed pronounced activity against Mycobacterium tuberculosis H(37)Rv and isoniazid resistant M. tuberculosis (INHR-TB) with minimum inhibitory concentrations (MICs) 0.78μM and 1.52 μM, respectively. The compound, 4a showed maximum activity against all bacterial strains with MIC 4-8 μg/mL comparable to standard drug ciprofloxacin, while the compounds, 4e and 4k showed maximum antifungal activity with MIC 8-16 μg/mL less active than standard drug fluconazole | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Anti-Infective Agents |2 NLM | |
| 650 | 7 | |a Antitubercular Agents |2 NLM | |
| 650 | 7 | |a Oxadiazoles |2 NLM | |
| 700 | 1 | |a Samy, Jeyabalan Govinda |e verfasserin |4 aut | |
| 700 | 1 | |a Khalilullah, Habibullah |e verfasserin |4 aut | |
| 700 | 1 | |a Nomani, Md Shivli |e verfasserin |4 aut | |
| 700 | 1 | |a Saraswat, Pankaj |e verfasserin |4 aut | |
| 700 | 1 | |a Gaur, Ramakant |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Abhimanyu |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Bioorganic & medicinal chemistry letters |d 1992 |g 21(2011), 24 vom: 15. Dez., Seite 7246-50 |w (DE-627)NLM09063828X |x 1464-3405 |7 nnns |
| 773 | 1 | 8 | |g volume:21 |g year:2011 |g number:24 |g day:15 |g month:12 |g pages:7246-50 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.bmcl.2011.10.057 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 21 |j 2011 |e 24 |b 15 |c 12 |h 7246-50 | ||