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Open AccessArticle

Novel Series of Methyl 3-(Substituted Benzoyl)-7-Substituted-2-Phenylindolizine-1-Carboxylates as Promising Anti-Inflammatory Agents: Molecular Modeling Studies

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Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
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Department of Biotechnology and Food Technology, Durban University of Technology, Durban 4001, South Africa
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Faculty of Pharmacy, Philadelphia University, Amman 19392, Jordan
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Department of Chemistry, Visvesvaraya National Institute of Technology, Nagpur, Maharashtra 440010, India
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Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia 61511, Egypt
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Department of Public Health Medicine, University of KwaZulu-Natal, Howard College Campus, Durban 4001, South Africa
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Department of Biomedical Sciences, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia
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Institute for Stem Cell Biology and Regenerative Medicine, NCBS, TIFR, GKVK, Bellary Road, Bangalore 560065, India
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Department of Pharmaceutical Sciences, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia
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Authors to whom correspondence should be addressed.
Biomolecules 2019, 9(11), 661; https://doi.org/10.3390/biom9110661
Received: 30 September 2019 / Revised: 22 October 2019 / Accepted: 23 October 2019 / Published: 28 October 2019
(This article belongs to the Section Chemical Biology)
The cyclooxygenase-2 (COX-2) enzyme is considered to be an important target for developing novel anti-inflammatory agents. Selective COX-2 inhibitors offer the advantage of lower adverse effects that are commonly associated with non-selective COX inhibitors. In this work, a novel series of methyl 3-(substituted benzoyl)-7-substituted-2-phenylindolizine-1-carboxylates was synthesized and evaluated for COX-2 inhibitory activity. Compound 4e was identified as the most active compound of the series with an IC50 of 6.71 μM, which is comparable to the IC50 of indomethacin, a marketed non-steroidal anti-inflammatory drug (NSAID). Molecular modeling and crystallographic studies were conducted to further characterize the compounds and gain better understanding of the binding interactions between the compounds and the residues at the active site of the COX-2 enzyme. The pharmacokinetic properties and potential toxic effects were predicted for all the synthesized compounds, which indicated good drug-like properties. Thus, these synthesized compounds can be considered as potential lead compounds for developing effective anti-inflammatory therapeutic agents. View Full-Text
Keywords: COX-2 inhibition; anti-inflammatory; indolizine derivatives; 2-phenyl indolizine; molecular modeling; absorption; distribution; metabolism; excretion; toxicity [ADMET] prediction COX-2 inhibition; anti-inflammatory; indolizine derivatives; 2-phenyl indolizine; molecular modeling; absorption; distribution; metabolism; excretion; toxicity [ADMET] prediction
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Venugopala, K.N.; Al-Attraqchi, O.H.; Tratrat, C.; Nayak, S.K.; Morsy, M.A.; Aldhubiab, B.E.; Attimarad, M.; Nair, A.B.; Sreeharsha, N.; Venugopala, R.; Haroun, M.; Girish, M.B.; Chandrashekharappa, S.; Alwassil, O.I.; Odhav, B. Novel Series of Methyl 3-(Substituted Benzoyl)-7-Substituted-2-Phenylindolizine-1-Carboxylates as Promising Anti-Inflammatory Agents: Molecular Modeling Studies. Biomolecules 2019, 9, 661.

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