Antibacterial study of 3-(2-amino-6-phenylpyrimidin-4-yl)-N-cyclopropyl-1-methyl-1H-indole-2-carboxamide derivatives: CoMFA, CoMSIA analyses, molecular docking and ADMET properties prediction

Zaki, Hanane; Belhassan, Assia; Aouidate, Adnane; Lakhlifi, Tahar; Benlyas, Mohamed; Bouachrine, Mohammed

doi:10.1016/j.molstruc.2018.09.073

Cited by 15 publications

(12 citation statements)

References 34 publications

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“…However, many computational and theoretical studies have been conducted by researchers to study and design indole 3-carboxamide derivatives, the results of which confirm previous studies [62,63]. In recent years, indole derivatives are shown to be active against many enzymes Renin [56] and proteins, indicating that these compounds are still in research [64][65][66][67].…”

Section: Renin Inhibitorssupporting

confidence: 72%

Synthetic strategies, SAR studies, and computer modeling of indole 2 and 3-carboxamides as the strong enzyme inhibitors: a review

Chehardoli

Bahmani

2020

Mol Divers

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Indole derivatives have been the focus of many researchers in the study of pharmaceutical compounds for many years. Researchers have investigated the effect of carboxamide moiety at positions 2 and 3, giving unique inhibitory properties to these compounds. The presence of carboxamide moiety in indole derivatives causes hydrogen bonds with a variety of enzymes and proteins, which in many cases, inhibits their activity. In this review, synthetic strategies of indole 2 and 3-carboxamide derivatives, the type, and mode of interaction of these derivatives against HLGP, HIV-1, renin enzyme, and structure-activity studies of these compounds were investigated. It is hoped that indole scaffolds will be tested in the future for maximum activity in pharmacological compounds.

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Section: Renin Inhibitorssupporting

confidence: 72%

Synthetic strategies, SAR studies, and computer modeling of indole 2 and 3-carboxamides as the strong enzyme inhibitors: a review

Chehardoli

Bahmani

2020

Mol Divers

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“…rac ‐ and meso ‐compounds 17 and 7 showed moderate activity against S. aureus. S. aureus , an adaptable pathogen, is multifaceted in nature and varies in severity of infection, affecting the skin, soft tissue, respiratory system, bone joints, and endovascular tissues . After the breakage of the epithelium, this extracellular pathogen bacteremia may cause serious diseases, such as pneumonia, osteomyelitis, endocarditis, and septic shock .…”

Section: Resultsmentioning

confidence: 99%

rac‐ and meso‐Cyclohexanoids: Their α‐, β‐glycosidases, antibacterial, antifungal activities, and molecular docking studies

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Baran

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et al. 2020

Archiv der Pharmazie

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An efficient and versatile synthesis method has been postulated for hydroxymethylated rac‐ and meso‐cyclohexanoid derivatives. The synthesis of these stereoisomers was achieved easily with traditional methods using hexahydroisobenzofuran 6, prepared from commercially available cis‐hydrophthalic anhydride. The study, involving diastereoselective epoxidation and cis‐hydroxylation, was conducted to obtain epoxy‐, cis‐, and trans‐diol‐furans 7, 8, and 9. After sulfamic acid‐catalyzed ring‐opening reaction of the epoxide and furan rings, rac‐ and meso‐tetraacetates 14, 15, and 16 were afforded. Hydrolysis of acetate groups with ammonia in absolute methanol yielded the desired tetrols rac‐17, meso‐18, and meso‐19. All structures, after purification by chromatographic methods and elucidation by spectral techniques, were screened against α‐ and β‐glucosidases. Compounds 7, 8, 10, 17, 18, and 19 were also evaluated for their antibacterial and antifungal activity against some selected synthesized compounds with varying degrees of inhibitory effects on the growth of different pathogenic microorganisms by the well‐diffusion method. In addition, Saccharomyces cerevisiae α‐glucosidase molecular modeling studies were performed for all rac‐ and meso‐compounds 7, 8, 10, 17, 18, and 19.

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“…All the synthesized compounds were purified by gravitational column chromatography and recrystallization techniques, followed by structural elucidation via spectroscopic analyses, including 1 H-, 13 C-, and 19 F-NMR, Fourier transform infra-red (FT-IR), and direct infusion-mass spectrometry (DI-MS), as well as high-resolution mass spectrometry (HRMS) for new molecules. The spectroscopic data of the newly synthesized analogues (5 and 11-15), general physical properties (Table S1), as well as the predicted physicochemical and drug-likeness properties (Table S2) of the synthesized molecules (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) were appended in Supplementary Materials.…”

Section: Chemistrymentioning

confidence: 99%

“…Bacterial infections are one of the significant threats to global health, mainly owing to the resistance of microorganisms towards antibiotics [ 1 ]. According to the Centre for Disease Control and Prevention (CDC) in the year 2017, more than 2 million diseases and 23,000 deaths occur annually due to antibiotic resistance in the United States.…”

Section: Introductionmentioning

confidence: 99%

Preliminary Insight of Pyrrolylated-Chalcones as New Anti-Methicillin-Resistant Staphylococcus aureus (Anti-MRSA) Agents

et al. 2021

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Bacterial infections are regarded as one of the leading causes of fatal morbidity and death in patients infected with diseases. The ability of microorganisms, particularly methicillin-resistant Staphylococcus aureus (MRSA), to develop resistance to current drugs has evoked the need for a continuous search for new drugs with better efficacies. Hence, a series of non-PAINS associated pyrrolylated-chalcones (1–15) were synthesized and evaluated for their potency against MRSA. The hydroxyl-containing compounds (8, 9, and 10) showed the most significant anti-MRSA efficiency, with the MIC and MBC values ranging from 0.08 to 0.70 mg/mL and 0.16 to 1.88 mg/mL, respectively. The time-kill curve and SEM analyses exhibited bacterial cell death within four hours after exposure to 9, suggesting its bactericidal properties. Furthermore, the docking simulation between 9 and penicillin-binding protein 2a (PBP2a, PDB ID: 6Q9N) suggests a relatively similar bonding interaction to the standard drug with a binding affinity score of −7.0 kcal/mol. Moreover, the zebrafish model showed no toxic effects in the normal embryonic development, blood vessel formation, and apoptosis when exposed to up to 40 µM of compound 9. The overall results suggest that the pyrrolylated-chalcones may be considered as a potential inhibitor in the design of new anti-MRSA agents.

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Antibacterial study of 3-(2-amino-6-phenylpyrimidin-4-yl)-N-cyclopropyl-1-methyl-1H-indole-2-carboxamide derivatives: CoMFA, CoMSIA analyses, molecular docking and ADMET properties prediction

Cited by 15 publications

References 34 publications

Synthetic strategies, SAR studies, and computer modeling of indole 2 and 3-carboxamides as the strong enzyme inhibitors: a review

Synthetic strategies, SAR studies, and computer modeling of indole 2 and 3-carboxamides as the strong enzyme inhibitors: a review

rac‐ and meso‐Cyclohexanoids: Their α‐, β‐glycosidases, antibacterial, antifungal activities, and molecular docking studies

Preliminary Insight of Pyrrolylated-Chalcones as New Anti-Methicillin-Resistant Staphylococcus aureus (Anti-MRSA) Agents

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