Cytotoxicity and Antimycobacterial Properties of Pyrrolo[1,2-<i>a</i>]quinoline Derivatives: Molecular Target Identification and Molecular Docking Studies
A series of ethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-<i>a</i>]quinoline-3-carboxylates <b>4a</b>–<b>f</b> and dimethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-<i>a</i>]quinoline-2,3-dicarboxylates <b>4g</b>–<b>k</b>...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | Antibiotics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6382/9/5/233 |
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doaj-f25c1a746c5a4cdb8c1931de74c7a524 |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Katharigatta N. Venugopala Vijayakumar Uppar Sandeep Chandrashekharappa Hassan H. Abdallah Melendhran Pillay Pran Kishore Deb Mohamed A. Morsy Bandar E. Aldhubiab Mahesh Attimarad Anroop B. Nair Nagaraja Sreeharsha Christophe Tratrat Abdulmuttaleb Yousef Jaber Rashmi Venugopala Raghu Prasad Mailavaram Bilal A. Al-Jaidi Mahmoud Kandeel Michelyne Haroun Basavaraj Padmashali |
| spellingShingle |
Katharigatta N. Venugopala Vijayakumar Uppar Sandeep Chandrashekharappa Hassan H. Abdallah Melendhran Pillay Pran Kishore Deb Mohamed A. Morsy Bandar E. Aldhubiab Mahesh Attimarad Anroop B. Nair Nagaraja Sreeharsha Christophe Tratrat Abdulmuttaleb Yousef Jaber Rashmi Venugopala Raghu Prasad Mailavaram Bilal A. Al-Jaidi Mahmoud Kandeel Michelyne Haroun Basavaraj Padmashali Cytotoxicity and Antimycobacterial Properties of Pyrrolo[1,2-<i>a</i>]quinoline Derivatives: Molecular Target Identification and Molecular Docking Studies Antibiotics pyrrolo[1,2-<i>a</i>]quinoline <i>Mycobacterium tuberculosis</i> H37Rv MDR-MTB minimum inhibitory concentration cytotoxicity |
| author_facet |
Katharigatta N. Venugopala Vijayakumar Uppar Sandeep Chandrashekharappa Hassan H. Abdallah Melendhran Pillay Pran Kishore Deb Mohamed A. Morsy Bandar E. Aldhubiab Mahesh Attimarad Anroop B. Nair Nagaraja Sreeharsha Christophe Tratrat Abdulmuttaleb Yousef Jaber Rashmi Venugopala Raghu Prasad Mailavaram Bilal A. Al-Jaidi Mahmoud Kandeel Michelyne Haroun Basavaraj Padmashali |
| author_sort |
Katharigatta N. Venugopala |
| title |
Cytotoxicity and Antimycobacterial Properties of Pyrrolo[1,2-<i>a</i>]quinoline Derivatives: Molecular Target Identification and Molecular Docking Studies |
| title_short |
Cytotoxicity and Antimycobacterial Properties of Pyrrolo[1,2-<i>a</i>]quinoline Derivatives: Molecular Target Identification and Molecular Docking Studies |
| title_full |
Cytotoxicity and Antimycobacterial Properties of Pyrrolo[1,2-<i>a</i>]quinoline Derivatives: Molecular Target Identification and Molecular Docking Studies |
| title_fullStr |
Cytotoxicity and Antimycobacterial Properties of Pyrrolo[1,2-<i>a</i>]quinoline Derivatives: Molecular Target Identification and Molecular Docking Studies |
| title_full_unstemmed |
Cytotoxicity and Antimycobacterial Properties of Pyrrolo[1,2-<i>a</i>]quinoline Derivatives: Molecular Target Identification and Molecular Docking Studies |
| title_sort |
cytotoxicity and antimycobacterial properties of pyrrolo[1,2-<i>a</i>]quinoline derivatives: molecular target identification and molecular docking studies |
| publisher |
MDPI AG |
| series |
Antibiotics |
| issn |
2079-6382 |
| publishDate |
2020-05-01 |
| description |
A series of ethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-<i>a</i>]quinoline-3-carboxylates <b>4a</b>–<b>f</b> and dimethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-<i>a</i>]quinoline-2,3-dicarboxylates <b>4g</b>–<b>k</b> have been synthesized and evaluated for their anti-tubercular (TB) activities against H37Rv (American Type Culture Collection (ATCC) strain 25177) and multidrug-resistant (MDR) strains of <i>Mycobacterium tuberculosis</i> by resazurin microplate assay (REMA). Molecular target identification for these compounds was also carried out by a computational approach. All test compounds exhibited anti-tuberculosis (TB) activity in the range of 8–128 µg/mL against H37Rv. The test compound dimethyl-1-(4-fluorobenzoyl)-5-methylpyrrolo[1,2-<i>a</i>]quinoline-2,3-dicarboxylate <b>4j</b> emerged as the most promising anti-TB agent against H37Rv and multidrug-resistant strains of <i>Mycobacterium tuberculosis</i> at 8 and 16 µg/mL, respectively. In silico evaluation of pharmacokinetic properties indicated overall drug-likeness for most of the compounds. Docking studies were also carried out to investigate the binding affinities as well as interactions of these compounds with the target proteins. |
| topic |
pyrrolo[1,2-<i>a</i>]quinoline <i>Mycobacterium tuberculosis</i> H37Rv MDR-MTB minimum inhibitory concentration cytotoxicity |
| url |
https://www.mdpi.com/2079-6382/9/5/233 |
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doaj-f25c1a746c5a4cdb8c1931de74c7a5242020-11-25T03:34:17ZengMDPI AGAntibiotics2079-63822020-05-01923323310.3390/antibiotics9050233Cytotoxicity and Antimycobacterial Properties of Pyrrolo[1,2-<i>a</i>]quinoline Derivatives: Molecular Target Identification and Molecular Docking StudiesKatharigatta N. Venugopala0Vijayakumar Uppar1Sandeep Chandrashekharappa2Hassan H. Abdallah3Melendhran Pillay4Pran Kishore Deb5Mohamed A. Morsy6Bandar E. Aldhubiab7Mahesh Attimarad8Anroop B. Nair9Nagaraja Sreeharsha10Christophe Tratrat11Abdulmuttaleb Yousef Jaber12Rashmi Venugopala13Raghu Prasad Mailavaram14Bilal A. Al-Jaidi15Mahmoud Kandeel16Michelyne Haroun17Basavaraj Padmashali18Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Chemistry, School of Basic Science, Rani Channamma University, Belagavi 591156, IndiaInstitute for Stem Cell Biology and Regenerative Medicine, National Center for Biological Sciences (NCBS), Tata Institute of Fundamental Research (TIFR), Gandhi Krishi Vignana Kendra (GKVK) Campus, Bangalore 560065, IndiaChemistry Department, College of Education, Salahaddin University, Erbil 44001, IraqDepartment of Microbiology, National Health Laboratory Services, KZN Academic Complex, Inkosi Albert Luthuli Central Hospital, Durban 4001, South AfricaFaculty of Pharmacy, Philadelphia University, Amman 19392, JordanDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaFaculty of Pharmacy, Philadelphia University, Amman 19392, JordanDepartment of Public Health Medicine, University of KwaZulu-Natal, Howard College Campus, Durban 4001, South AfricaDepartment of Pharmaceutical Chemistry, Shri Vishnu College of Pharmacy, Vishnupur, Bhimavaram 534 202, IndiaFaculty of Pharmacy, Yarmouk University, Irbid 21163, JordanDepartment of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Chemistry, School of Basic Science, Rani Channamma University, Belagavi 591156, IndiaA series of ethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-<i>a</i>]quinoline-3-carboxylates <b>4a</b>–<b>f</b> and dimethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-<i>a</i>]quinoline-2,3-dicarboxylates <b>4g</b>–<b>k</b> have been synthesized and evaluated for their anti-tubercular (TB) activities against H37Rv (American Type Culture Collection (ATCC) strain 25177) and multidrug-resistant (MDR) strains of <i>Mycobacterium tuberculosis</i> by resazurin microplate assay (REMA). Molecular target identification for these compounds was also carried out by a computational approach. All test compounds exhibited anti-tuberculosis (TB) activity in the range of 8–128 µg/mL against H37Rv. The test compound dimethyl-1-(4-fluorobenzoyl)-5-methylpyrrolo[1,2-<i>a</i>]quinoline-2,3-dicarboxylate <b>4j</b> emerged as the most promising anti-TB agent against H37Rv and multidrug-resistant strains of <i>Mycobacterium tuberculosis</i> at 8 and 16 µg/mL, respectively. In silico evaluation of pharmacokinetic properties indicated overall drug-likeness for most of the compounds. Docking studies were also carried out to investigate the binding affinities as well as interactions of these compounds with the target proteins.https://www.mdpi.com/2079-6382/9/5/233pyrrolo[1,2-<i>a</i>]quinoline<i>Mycobacterium tuberculosis</i>H37RvMDR-MTBminimum inhibitory concentrationcytotoxicity |