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1.
Molecules ; 24(19)2019 Sep 26.
Article in English | MEDLINE | ID: mdl-31561635

ABSTRACT

New 1,4-disubstituted ß-pyrrolidino-1,2,3-triazoles were synthesized using a reusable copper-iodide-doped neutral alumina catalyst. Synthesis of diversely substituted triazoles and recyclability of CuI catalyst explains the broad scope of this protocol. The synthesized compounds were screened for their antimicrobial and anticancer properties. Most of the compounds showed significant antimicrobial activities against all the tested microorganisms compared to standard drugs. Furthermore, compounds 5a, 5e, 5g, 5h, 5i, and 5j showed moderate to potent activities against A549 and HepG-2 cells. In addition, compounds 5g and 5h displayed potential cytotoxicity activity against A549 cells with IC50 values of 72 ± 3.21 and 58 ± 2.31 µM, respectively. The molecular docking study revealed that some of the synthesized compounds exhibited comparable binding as co-crystalized ligands with the DNA topoisomerase IV and anaplastic lymphoma kinase receptors.


Subject(s)
Adrenergic beta-Antagonists/chemical synthesis , Adrenergic beta-Antagonists/pharmacology , Triazoles/chemical synthesis , Triazoles/pharmacology , Adrenergic beta-Antagonists/chemistry , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Chemistry Techniques, Synthetic , Dose-Response Relationship, Drug , Humans , Microbial Sensitivity Tests , Molecular Conformation , Molecular Docking Simulation , Molecular Dynamics Simulation , Molecular Structure , Protein Binding , Receptors, Adrenergic, beta-2/chemistry , Structure-Activity Relationship , Triazoles/chemistry
2.
Bioorg Chem ; 91: 103180, 2019 10.
Article in English | MEDLINE | ID: mdl-31416031

ABSTRACT

Novel cage-like indolizine-acenaphthene-pyridinone heterocyclic hybrids were synthesized in good yields through [bmim]Br mediated tandem 1,3-dipolar cycloaddition-annulation sequence. The anti-inflammatory activity of these hybrids was performed using carrageenan-induced hind paw oedema, croton oil-induced ear oedema and cotton pellet-induced granuloma models. Four of these cage-like heterocyclic hybrids viz. 4b, 4d, 4e and 4j showed substantial anti-inflammatory activities against acute and chronic inflammatory models and also showed significant inhibition of PGE2, TNF-α, and nitrite levels in carrageenan-induced hind paw oedema.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Dinoprostone/antagonists & inhibitors , Drug Discovery , Edema/drug therapy , Granuloma/drug therapy , Heterocyclic Compounds/chemistry , Nitrites/antagonists & inhibitors , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Anti-Inflammatory Agents/chemistry , Carrageenan/toxicity , Edema/chemically induced , Edema/pathology , Granuloma/chemically induced , Granuloma/pathology , Mice , Rats , Rats, Wistar
3.
Molecules ; 24(10)2019 May 22.
Article in English | MEDLINE | ID: mdl-31121813

ABSTRACT

An expedient synthesis of hitherto unexplored novel hybrid heterocycles comprising dispiropyrrolidine, N-styrylpiperidone and indeno[1,2-b]quinoxaline units has been developed via domino multicomponent 1,3-dipolar cycloaddition strategy employing a new class of azomethine ylide in ionic liquid, 1-butyl-3-methylimidazolium bromide. This domino protocol involves, 1,3-dipolar cycloaddition and concomitant enamine reaction affording the dispiropyrrolidine tethered N-styrylpiperidone hybrid heterocycles in moderate to good yield in a single step. These compounds were evaluated for their antimicrobial activity against bacterial and fungal pathogens, therein compounds 8f, 8h, and 8l displayed significant activity against tested microbial pathogens. The synergistic effect revealed that the combination of compound 8h with streptomycin and vancomycin exhibited potent synergistic activity against E. coli ATCC 25922. In addition, molecular docking simulation has also been studied for the most active compound.


Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Quinoxalines/chemical synthesis , Quinoxalines/pharmacology , Anti-Bacterial Agents/chemistry , Cycloaddition Reaction , Drug Synergism , Escherichia coli/drug effects , Imidazoles/chemistry , Microbial Sensitivity Tests , Molecular Docking Simulation , Molecular Structure , Quinoxalines/chemistry , Streptomycin/pharmacology , Structure-Activity Relationship , Vancomycin/pharmacology
4.
Chem Cent J ; 12(1): 95, 2018 Sep 01.
Article in English | MEDLINE | ID: mdl-30173362

ABSTRACT

BACKGROUND: Spiropyrrolidine tethered piperidone heterocyclic hybrids were synthesized with complete regio- and stereoselectively in excellent yield via a tandem three-component 1,3-dipolar cycloaddition and subsequent enamine reaction in [bmim]Br. The synthesized compounds were evaluated for their anticancer activity against FaDu hypopharyngeal tumor cells. FINDINGS: Interestingly, most compounds displayed cytotoxicities similar to the standard anticancer agent bleomycin, with two of them (5a and 5g) being slightly more active than the reference drug. CONCLUSION: Synthesized compounds have also been evaluated for their apoptosis-inducing properties in a cancer cell model, finding that treatment with compounds 5a-e led to apoptotic cell death.

5.
Bioorg Chem ; 81: 134-143, 2018 12.
Article in English | MEDLINE | ID: mdl-30121001

ABSTRACT

Novel highly functionalized 2-amino-4H-pyrans were achieved in excellent yields under simple grinding at ambient temperature and were assessed for their potential for treating Alzheimer's disease (AD). The 2-amino-4H-pyran bearing nitro groups on both the aryl rings showed the highest activity, with an IC50 of 1.98 ±â€¯0.09 µM against acetylcholinesterase (AChE) and 10.62 ±â€¯0.21 µM against butyrylcholinesterase (BChE), the inhibition mechanisms on AChE and BChE receptors were revealed by means of molecular docking simulations.


Subject(s)
Acetylcholinesterase/metabolism , Butyrylcholinesterase/metabolism , Cholinesterase Inhibitors/pharmacology , Pyrans/pharmacology , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/chemistry , Dose-Response Relationship, Drug , Humans , Molecular Docking Simulation , Molecular Structure , Pyrans/chemical synthesis , Pyrans/chemistry , Structure-Activity Relationship
6.
Molecules ; 23(5)2018 May 05.
Article in English | MEDLINE | ID: mdl-29734741

ABSTRACT

A series of spirooxindolopyrrolidine fused N-styrylpiperidone heterocyclic hybrids has been synthesized in excellent yield via a domino multicomponent protocol that involves one-pot three component 1,3-dipolar cycloaddition and concomitant enamine reactions performed in an inexpensive ionic liquid, namely 1-butyl-3-methylimidazolium bromide ([bmim]Br). Compounds thus synthesized were evaluated for their cytotoxicity against U-937 tumor cells. Interestingly; compounds 5i and 5m exhibited a better cytotoxicity than the anticancer drug bleomycin. In addition; the effect of the synthesized compounds on the nuclear morphology of U937 FaDu cells revealed that treatment with compounds 5a⁻m led to their apoptotic cell death.


Subject(s)
Antineoplastic Agents/chemical synthesis , Indoles/chemical synthesis , Piperidones/chemical synthesis , Proto-Oncogene Proteins c-met/antagonists & inhibitors , Pyrrolidines/chemical synthesis , Spiro Compounds/chemical synthesis , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Binding Sites , Bleomycin/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Cycloaddition Reaction , Drug Design , Humans , Imidazoles/chemistry , Indoles/pharmacology , Inhibitory Concentration 50 , Lymphocytes/drug effects , Lymphocytes/pathology , Molecular Docking Simulation , Piperidones/pharmacology , Protein Binding , Protein Interaction Domains and Motifs , Protein Structure, Secondary , Proto-Oncogene Proteins c-met/chemistry , Proto-Oncogene Proteins c-met/metabolism , Pyrrolidines/pharmacology , Spiro Compounds/pharmacology , Structure-Activity Relationship
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