Hydroxyenone Derivatives: In vitro Anti-malarial and Docking Studies against P. falciparum

2020 ◽  
Vol 20 (2) ◽  
pp. 237-243 ◽  
Author(s):  
Aarti Dalal ◽  
Parvin Kumar ◽  
Radhika Khanna ◽  
Dinesh Kumar ◽  
Deepika Paliwal ◽  
...  
Keyword(s):  
Molecular Docking ◽  
13C Nmr ◽  
Antimalarial Activity ◽  
Docking Studies ◽  
Binding Energies ◽  
Spectral Studies ◽  
Mass Analysis ◽  
Autodock Vina ◽  
Ft Ir

Methods: A series of 1-2-(prop-2-ynyloxy)aryl-3-hydroxy-3-(4'-trifluoromethylphenyl) prop-2-en-1-ones obtained by photo-irradiation of 2-2-(prop-2-ynyloxy)benzoyl-3-(4- trifluorome-thyl-phenyl)oxiranes (that were characterized by spectral studies: FT-IR, 1H NMR, 13C NMR and Mass analysis) was screened for the anti-malarial activity by evaluating against chloroquine-sensitive P. falciparum (CD7). The molecular docking studies using AutoDock Vina were also performed to further ascertain the efficacy of these compounds with PDB:4ORM. Results: Among these, the hydroxyenone derivatives 2b, 2c and 2a exhibited very potent antimalarial activity that was clearly evinced by the results of molecular docking. Binding energies of hydroxyenone compounds were calculated and found in the range of -10.4 to -9.0 kcal/mol. Conclusion: Compound 2b had the strongest binding affinity with docking score of -10.4 kcal/mol.

scholarly journals Synthesis, antimicrobial and antimalarial activityof1, 4-benzothiazepine and pyrazolinederivatives incorporating carbazolemoiety

2019 ◽  
Vol 51 (2) ◽  
pp. 234-241
Author(s):  
V. A. Kadnor ◽  
S. N. Shelke
Keyword(s):  
Antimicrobial Activity ◽  
Antifungal Activity ◽  
13C Nmr ◽  
Antimalarial Activity ◽  
Positive Control ◽  
Spectral Studies ◽  
Standard Drug ◽  
Mass Spectral ◽  
Ft Ir

A series of carbazole-based 1,4-benzothiazepine and pyrazoline derivatives were synthesized and the structures of the newly synthesized compounds were confirmed by FT-IR, 1H NMR, 13C NMR and mass spectral studies. All new derivatives 4(a-f) and 5(a-e) were screened for their in vitro antimicrobial activity, and also for their antimalarial activity. Compounds 4a, 4b, 4d, 5a, 5b and 5c exhibited promising antimicrobial and antimalarial activities as compared to positive control. Notably, compounds 4a, 4b and 4d showed excellent antifungal activity against Penicillium sp. comparable to that of a standard drug.

scholarly journals Synthesis, antimalarial activity evaluation and molecular docking studies of some novel dispiro-1,2,4,5-tetraoxanes

2015 ◽  
Vol 10 (4) ◽  
pp. 917 ◽  
Author(s):  
Mukesh Kumar Kumawat ◽  
Dipak Chetia
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Docking ◽  
Resistant Strain ◽  
Antimalarial Activity ◽  
Binding Pocket ◽  
Docking Studies ◽  
Spectroscopic Techniques ◽  
Molecular Docking Studies ◽  
Activity Screening

<p class="Abstract">Seven novel dispiro-1,2,4,5-tetraoxane derivatives were synthesized and characterized by a number of analytical and spectroscopic techniques. The molecules were subsequently screened for in vitro antimalarial activity against chloroquine resistant strain of <em>Plasmodium falciparum</em> (RKL-9). At antimalarial activity screening, two compounds, namely 5d (MIC = 15.6 µg/mL or 64.5 µM) and 5f (MIC = 15.6 µg/mL or 54.6 µM) were found to be about 1.5 times more potent against chloroquine resistant strain-RKL-9 compared to chloroquine (MIC = 25.0 µg/mL or 78.3 µM). Molecular docking studies of potent ligands were also performed in cysteine protease binding pocket residues of falcipain-2 as a target protein.</p><p> </p>

scholarly journals Synthesis, Antimalarial Activity, and Docking Studies of Monocarbonyl Analogues of Curcumin

2018 ◽  
Vol 29 (2) ◽  
pp. 92-96
Author(s):  
Amina S. Yusuf ◽  
Ibrahim Sada ◽  
Yusuf Hassan ◽  
Temitope O. Olomola ◽  
Christiana M. Adeyemi ◽  
...  
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Antimalarial Activity ◽  
Docking Studies ◽  
Aryl Ring ◽  
Molecular Docking Studies ◽  
Plasmodium Parasite

Abstract The synthesis of five monocarbonyl analogues of curcumin is described. In vitro anti-malarial assay of the compounds was carried out and the effect of the substituents on the aryl ring has been described. The results show that all the five compounds exhibited some reasonable activity against the chloroquine-resistant plasmodium parasite. Molecular docking studies further confirmed the observed biological activity of the compounds.

Pyrazole Schiff Base Hybrids as Anti-Malarial Agents: Synthesis, In Vitro Screening and Computational Study

2018 ◽  
Vol 21 (3) ◽  
pp. 194-203 ◽  
Author(s):  
Shilpy Aggarwal ◽  
Deepika Paliwal ◽  
Dhirender Kaushik ◽  
Girish Kumar Gupta ◽  
Ajay Kumar
Keyword(s):  
Schiff Base ◽  
Antimalarial Activity ◽  
Computational Study ◽  
Docking Study ◽  
Docking Studies ◽  
Binding Energies ◽  
Study Results ◽  
Wide Range ◽  
Parasite Plasmodium Falciparum

Background: Malaria is one of the most vital infectious diseases caused by protozoan parasites of the Plasmodium genus. As P. falciparum, the cause of most of the severe cases of malaria, is increasingly resistant to available drugs such as amodioquine, chloroquine, artemisinin, and antifolates, there is an urgent need to identify new targets for chemotherapy. Objective: This study screened novel pyrazole derivatives carrying iminium & benzothiazole group for antimalarial potential against P. falciparum chloroquine sensitive (3D7) strain. Materials & Methods: Several pyrazole schiff base hybrids with a wide range of substitution have been synthesized via condensation of substituted aniline with substituted 4-formylpyrazole and evaluated for their in vitro antimalarial activity against asexual blood stages of human malaria parasite, Plasmodium falciparum. The interaction of these conjugate hybrids was also investigated by molecular docking studies in the binding site of P. falciparum cystein protease falcipain-2. The pharmacokinetic properties were also studied using ADME prediction. Results: Among all compounds, 6bf and 6bd were found to be potential molecules with EC50 1.95µg/ml and 1.98µg/ml respectively. Docking study results reveal that the pyrazole schiff base derivatives occupy the PfFP binding sites and they show good interactions with significant values of binding energies. Conclusion: We provide evidence which implicates pyrazole Schiff base hybrids as potential prototypes for the development of antimalarial agents.

Antioxidant, Antimicrobial, Molecular Docking Studies of Novel 2,6-bis(1,3-Thiazol-2-yl)-4-(3,4,5-trimethoxyphenyl)pyridine and its Cu(II) and Ni(II) Complexes

2020 ◽  
Vol 5 (2) ◽  
pp. 103-108
Author(s):  
Madavi Sunitha ◽  
G. Venkateshappa ◽  
G. Ramesh ◽  
Jayanna Kengaiah ◽  
G. Shivaraja ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antioxidant Activity ◽  
Molecular Docking ◽  
Metal Complexes ◽  
13C Nmr ◽  
Human Erythrocyte ◽  
Esr Spectra ◽  
Docking Studies ◽  
Ft Ir ◽  
Parent Ligand

In the present study, a novel ligand 2,6-bis(1,3-thiazol-2-yl)-4-(3,4,5-trimethoxyphenyl)pyridine and its Cu(II) and Ni(II) complexes were synthesized. All the synthesized compounds have been characterized by 1H & 13C NMR, mass, UV, FT-IR and ESR spectra. The antioxidant activity of the ligand and its Cu(II) and Ni(II) complexes were evaluated by the percentage of inhibition of 1,1-diphenyl- 2-picryl hydrazyl (DPPH) and compounds found to be potent antioxidants. Also, synthesized compounds showed a mild antimicrobial activity in comparison with standard drugs. Copper(II) complexes showed a good antimicrobial activity than the parent ligand and nickel(II) complex. Interestingly, ligand and its metal complexes exhibit non-toxicity as they did not cause any effect to human erythrocyte.

scholarly journals Phloroglucinol as a Potential Candidate against Trypanosoma congolense Infection: Insights from In Vivo, In Vitro, Molecular Docking and Molecular Dynamic Simulation Analyses

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 469
Author(s):  
Nasirudeen Idowu Abdulrashid ◽  
Suleiman Aminu ◽  
Rahma Muhammad Adamu ◽  
Nasir Tajuddeen ◽  
Murtala Bindawa Isah ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Binding Energies ◽  
Sub Saharan Africa ◽  
Dynamics Simulation ◽  
Potential Candidate ◽  
Inhibitory Effects ◽  
Hydrogen Bond Interaction

Sub-Saharan Africa is profoundly challenged with African Animal Trypanosomiasis and the available trypanocides are faced with drawbacks, necessitating the search for novel agents. Herein, the chemotherapeutic potential of phloroglucinol on T. congolense infection and its inhibitory effects on the partially purified T. congolense sialidase and phospholipase A2 (PLA2) were investigated. Treatment with phloroglucinol for 14 days significantly (p < 0.05) suppressed T. congolense proliferation, increased animal survival and ameliorated anemia induced by the parasite. Using biochemical and histopathological analyses, phloroglucinol was found to prevent renal damages and splenomegaly, besides its protection against T. congolense-associated increase in free serum sialic acids in infected animals. Moreover, the compound inhibited bloodstream T. congolense sialidase via mixed inhibition pattern with inhibition binding constant (Ki) of 0.181 µM, but a very low uncompetitive inhibitory effects against PLA2 (Ki > 9000 µM) was recorded. Molecular docking studies revealed binding energies of −4.9 and −5.3 kcal/mol between phloroglucinol with modeled sialidase and PLA2 respectively, while a 50 ns molecular dynamics simulation using GROMACS revealed the sialidase-phloroglucinol complex to be more compact and stable with higher free binding energy (−67.84 ± 0.50 kJ/mol) than PLA2-phloroglucinol complex (−77.17 ± 0.52 kJ/mol), based on MM-PBSA analysis. The sialidase-phloroglucinol complex had a single hydrogen bond interaction with Ser453 while none was observed for the PLA2-phloroglucinol complex. In conclusion, phloroglucinol showed moderate trypanostatic activity with great potential in ameliorating some of the parasite-induced pathologies and its anti-anemic effects might be linked to inhibition of sialidase rather than PLA2.

Mechanochemical Synthesis, in vitro Evaluation and Molecular Docking Studies of 4-Amino-2-arylamino-5-(benzofuran-2-oyl)thiazoles as Antidiabetic Agents

2019 ◽  
Vol 16 (7) ◽  
pp. 560-568
Author(s):  
Vijayan R. Akhila ◽  
Maheswari R. Priya ◽  
Daisy R. Sherin ◽  
Girija K. Krishnapriya ◽  
Sreerekha V. Keerthi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Mechanochemical Synthesis ◽  
Active Sites ◽  
Docking Studies ◽  
Binding Energies ◽  
Antidiabetic Activity ◽  
Antidiabetic Agents ◽  
Molecular Docking Studies ◽  
Ic50 Value

The synthesis of 4-amino-2-arylamino-5-(benzofuran-2-oyl)thiazoles 4a-h, as example of 2,4-diaminothiazole-benzofuran hybrids and an evaluation of their antidiabetic activity, by in vitro and computational methods, are reported. The synthesis of these diaminothiazoles was achieved mechano chemically by a rapid solvent-less method. Their antidiabetic activity was assessed by &#945;-glucosidase and &#945;-amylase inhibition assays. The, IC50 value for &#945;-glucosidase inhibition by 4-amino-5- (benzofuran-2-oyl)-2-(4-methoxyphenylamino)thiazole (4d) was found to be 20.04 &#181;M and the IC50 value for &#945;-amylase inhibition, 195.03 &#181;M, whereas the corresponding values for reference acarbose were 53.38 &#181;M and 502.03 &#181;M, respectively. Molecular docking studies at the active sites of &#945;- glucosidase and α-amylase showed that among the diaminothiazoles 4a-h now studied, 4-amino-5- (benzofuran-2-oyl)-2-(4-methoxyphenylamino)thiazole (4d) has the highest D-scores of -8.63 and -8.08 for &#945;-glucosidase and for α-amylase, with binding energies -47.76 and -19.73 kcal/mol, respectively.

scholarly journals Synthesis and Biological Evaluation of Alanine Derived Bioactive p-Toluenesulphonamide Analogs

2020 ◽  
Vol 11 (4) ◽  
pp. 6449-6458
Author(s):  
Melford C Egbujor ◽  
Uchechukwu C Okoro ◽  
Samuel A Egu ◽  
Pius I Egwuatu ◽  
Florence U Eze ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antimalarial Activity ◽  
Biological Activities ◽  
Analytical Data ◽  
Antioxidant Properties ◽  
Antimicrobial Properties ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Agar Dilution

Sulphonamides and carboxamides have great pharmacological importance. The purpose of the study was to synthesize alanine-derived bioactive sulphonamides bearing carboxamides and evaluate their biological activities. The reaction of p-toluenesulphonyl chloride with L-alanine afforded compound 1, which was acetylated to obtain compound 2. The chlorination and ammonolysis of compound 2 gave the carboxamide backbone (3) which was coupled with aryl/heteroaryl halides to afford the hybrid compounds 4, 5 and 6. Structures were confirmed by FTIR, 1H-NMR, 13C-NMR spectra and elemental analytical data. The in vitro antimicrobial properties were determined by agar dilution, and the antioxidant properties were also investigated. Molecular docking interactions of the analogues were determined using PyRx. Compounds 4, 5 and 6 exhibited excellent in vitro antimicrobial properties in the range of 0.5-1.0mg/ml while compounds 1and 2 had half-maximal inhibitory concentration (IC50) of 1.11±0.15µg/ml and 1.12±0.13µg/ml respectively. For the molecular docking studies, compounds 5 and 6 displayed the best antitrypanosomal activity with binding affinities of -13.95 and -13.51kcal/mol respectively while compound 4 showed the highest in silico antimalarial activity having binding affinity of -11.95kcal/mol. All the alanine derived sulphonamides were observed to be potential antimicrobial, antioxidant, antitrypanosomal and antimalarial agents following the biological activities studies.

scholarly journals Synthesis, biological evaluation and molecular docking studies of new 2-ethoxy-4-{[3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl]-azomethine}-phenyl benzenesulfonate derivatives on human aldose reductase enzyme

2021 ◽  
Author(s):  
Gül Özdemir ◽  
Namık Kılınç ◽  
Sevda Manap ◽  
Murat Beytur ◽  
Muzaffer Alkan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antibacterial Activities ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Binding Energies ◽  
Diffusion Method ◽  
Alkyl Aryl ◽  
Molecular Docking Studies ◽  
New Compounds

A series of 2-ethoxy-4-{[3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl]-azomethine}-phenyl benzenesulfonates (3) were synthesized from the reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (1) with 2-ethoxy-4-formyl-phenyl benzenesulfonate (2). N-acetyl derivatives (4) of compounds 3 were also obtained. Then, the compounds 3 have been treated with morpholine and 2,6-dimethylmorpholine in the presence of formaldehyde to synthesize 2-ethoxy-4-{[1-(morpholine-4-yl-methyl)-3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl]-azomethine}-phenyl benzenesulfonates (5) and 2-ethoxy-4-{[1-(2,6-dimethylmorpholine-4-yl-methyl)-3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl]-azomethine}-phenyl benzenesulfonates (6), respectively. The structures of twenty-six new compounds were identified by using elemental analysis, IR, 1H NMR, 13C NMR, and MS spectral data. In addition, in vitro antibacterial activities of the new compounds were evaluated against six bacteria such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Bacillus cereus and Klepsiella pneumonia according to agar well diffusion method. Furthermore, in order to determine the possible antidiabetic properties of the synthesized 1,2,4-triazole derivatives, inhibition effects on the AR enzyme were investigated and molecular docking studies were carried out to determine the receptor-ligand interactions of these compounds. IC50 values of triazole-derived compounds (6a, 6b, 6d-g) against AR enzyme were determined as 0.95 µM, 0.75 µM, 1.83 µM, 0.62 µM, 1.05 µM, 1.06 µM, respectively. Considering the docking scores and binding energies obtained docking studies, it has been shown that molecules fit very well to the active site of the AR enzyme.

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