Crystal, Hirshfeld, ADMET, drug-like and anticancer study of some newly synthesized imidazopyridine containing pyrazoline derivatives

Kuthyala, Sharanya; Hanumanthappa, Manjuanatha; Kumar, Shankar; Sheik, Sana; Karikannar, Nagaraja Gundibasappa; Prabhu, Ashwini

doi:10.1016/j.molstruc.2019.07.031

Cited by 22 publications

(12 citation statements)

References 16 publications

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“…Apart from these efforts, a very limited number of related compounds have been prepared and reported which, however, have either shown no activity at all, being far less active than their precursors [ 139 ], or they display IC 50 values over 40 μM against tested cell lines [ 140 ], or, in some cases, their activities are not reported at all, presumably due to the lack of it [ 141 ]. Nevertheless, compound 63 ( Figure 22 ) incorporating a structurally interesting imidazoquinonyl moiety has shown low cytotoxicity against HeLa cancer cells (IC 50 = 15.1 μM), slightly higher than its chalcone precursor or N -phenyl pyrazoline analogue [ 142 ].…”

Section: 2-pyrazolinesmentioning

confidence: 99%

Pyrazoline Hybrids as Promising Anticancer Agents: An Up-to-Date Overview

Matiadis

Sagnou

2020

IJMS

104

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Pyrazolines are five-membered heterocycles possessing two adjacent nitrogens. They have attracted significant attention from organic and medicinal chemists due to their potent biological activities and the numerous possibilities for structural diversification. In the last decade, they have been intensively studied as targets for potential anticancer therapeutics, producing a steady yearly rise in the number of published research articles. Many pyrazoline derivatives have shown remarkable cytotoxic activities in the form of heterocyclic or non-heterocyclic based hybrids, such as with coumarins, triazoles, and steroids. The enormous amount of related literature in the last 5 years prompted us to collect all these published data from screening against cancer cell lines, or protein targets like EGFR and structure activity relationship studies. Therefore, in the present review, a comprehensive account of the compounds containing the pyrazoline nucleus will be provided. The chemical groups and the structural modifications responsible for the activity will be highlighted. Moreover, emphasis will be given on recent examples from the literature and on the work of research groups that have played a key role in the development of this field.

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Section: 2-pyrazolinesmentioning

confidence: 99%

Pyrazoline Hybrids as Promising Anticancer Agents: An Up-to-Date Overview

Matiadis

Sagnou

2020

IJMS

104

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“…The hepatotoxicity levels of the plant and microbial transformation products of QNs and their derivatives were predicted based on pharmacokinetics using the ADMET module of the DS software (BIOVIA Inc., Shenzhen, China) [79,80]. In addition, the potential risks to human health raised by these transformation products were predicted based on toxicokinetics using the 10 toxicity models in the TOPKAT module of the DS software [81], including the developmental toxicity potential (DTP), skin sensitization, skin irritancy, ocular irritancy, mutagenicity (Ames Test), rodent carcinogenicity (NTP and FDA datasets), and rat oral toxicity (LD 50 ), etc.…”

Section: Assessment Of Human Health Risk Raised By the Plant And Microbial Transformation Products Of Qns And Their Derivatives Using Phamentioning

confidence: 99%

Strategies to Control Human Health Risks Arising from Antibiotics in the Environment: Molecular Modification of QNs for Enhanced Plant–Microbial Synergistic Degradation

Sun

Zhao

2021

IJERPH

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In the present work, a comprehensive screening and evaluation system was established to improve the plant–microbial synergistic degradation effects of QNs. The study included the construction of a 3D-QSAR model, the molecular modification, environmental friendliness and functional evaluation of drugs, degradation pathway simulation, and human health risk assessment. Molecular dynamics was applied to quantify the binding capacity of QNs toward the plant degradation enzyme (peroxidase) and microbial degradation enzymes (manganese peroxidase, lignin peroxidase, and laccase). The fuzzy comprehensive evaluation method was used in combination with the weighted average method for normalization and assigning equal weights to the plant and microbial degradation effect values of the QNs. Considering the synergistic degradation effect value as the dependent variable and the molecular information of the QNs as the independent variable, a 3D-QSAR model was constructed for the plant–microbial synergistic degradation effect of QNs. The constructed model was then employed to conduct the molecular modification, environmental friendliness and functional evaluation, degradation pathway simulation, and human health risk assessment of transformation products using pharmacokinetics and toxicokinetics. The results revealed that the synergistic degradation effect 3D-QSAR (CoMSIA) model exhibited good internal and external prediction ability, fitting ability, stability, and no overfitting phenomenon. Norfloxacin (NOR) was used as the target molecule in the molecular modification. A total of 35 NOR derivatives with enhanced plant–microbial synergistic degradation effect (1.32–21.51%) were designed by introducing small-volume, strongly electronegative, and hydrophobic hydrogen bond receptor groups into the active group of the norfloxacin structure. The environment-friendliness and the functionality of NOR were evaluated prior to and after the modification, which revealed seven environment-friendly FQs derivatives exhibiting moderate improvement in stability and bactericidal efficacy. The simulation of the NOR plant and microbial degradation pathways prior to and after the modification and the calculation of the reaction energy barrier revealed Pathway A (D-17 to D-17-2) and Pathway B (D-17 to D-17-4) as the most prone degradation pathways in plants and Pathway A (D-17 to D-17-1) and Pathway B (D-17 to D-17-4) as the most prone degradation pathways in microorganisms. This demonstrated that the degradation of the modified NOR derivatives was significantly enhanced, with the hydroxylation and piperazine ring substitution reaction playing an important role in the degradation process. Finally, the parameters, including hepatotoxicity, mutagenicity, and rodent carcinogenicity, among others, predicted using the pharmacokinetics and toxicokinetics analyses revealed a significant reduction in the human health risk associated with the modified NOR, along with a considerable reduction in the toxicity of its transformation products, implying that the human health risk associated with the transformation products was reduced remarkably. The present study provides a theoretical basis for novel ideas and evaluation programs for improving the plant–microbial synergistic degradation of the QNs antibiotics for source control and drug design, thereby reducing the residues of these antibiotics and the associated hazard in the complex plant–soil environment, ultimately decreasing the potential risks to human health.

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“…Pyrazole, first isolated from watermelon seeds, is an active heterocycle used as an antimicrobial, [ 3 ] antiviral, [ 4 ] antitubercular, [ 5 ] anticancer, [ 6 ] analgesic and anti‐inflammatory [ 7 ] agents. Pyrazoline is dihydropyrazole possessed anticancer, [ 8 ] anti‐inflammatory [ 9 ] and antimalarial [ 10 ] activity, etc. Pyridine is also an important heterocycle in medicinal chemistry and is associated with several pharmaceutical activities.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, biological evaluation, and molecular docking studies of novel pyrazole, pyrazoline‐clubbed pyridine as potential antimicrobial agents

Desai

Vaja

Monapara

et al. 2021

Journal of Heterocyclic Chem

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We have prepared 15 hybrid pyrazole, pyrazoline‐clubbed pyridine–containing compounds (5a‐o) and tested for their antibacterial and antifungal activities for the development of potential antimicrobial agents. The structures of this novel series were characterized by various spectral techniques like IR, 1H NMR, 13C NMR, LC–MS, and elemental analysis. The synthesized compounds 5d, 5e, 5i, 5k, 5m, and 5o exhibited significant antimicrobial activity in the comparison of standard drugs. Molecular docking studies that have been carried out to emphasize the binding orientations of these molecules were in good compliance with crystal structure interactions. The predicted drug‐likeness (ADME) properties were found to be in the acceptable range.

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Crystal, Hirshfeld, ADMET, drug-like and anticancer study of some newly synthesized imidazopyridine containing pyrazoline derivatives

Cited by 22 publications

References 16 publications

Pyrazoline Hybrids as Promising Anticancer Agents: An Up-to-Date Overview

Pyrazoline Hybrids as Promising Anticancer Agents: An Up-to-Date Overview

Strategies to Control Human Health Risks Arising from Antibiotics in the Environment: Molecular Modification of QNs for Enhanced Plant–Microbial Synergistic Degradation

Synthesis, biological evaluation, and molecular docking studies of novel pyrazole, pyrazoline‐clubbed pyridine as potential antimicrobial agents

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