Synthesis, Biological Screening and Docking Study of Some Novel Pyrazolopyrano[2,3-B]quinolin Derivatives as Potent Antibacterial Agents

2022 ◽  
Vol 18 ◽  
Author(s):  
Hamideh. Emtiazi ◽  
Ali Salari Sharif ◽  
Mina Ardestani
Keyword(s):  
Staphylococcus Aureus ◽  
Molecular Docking ◽  
Hydrophobic Interactions ◽  
Biological Activities ◽  
Aromatic Aldehydes ◽  
Dna Gyrase ◽  
Docking Study ◽  
Antibacterial Activities ◽  
Synthetic Methods ◽  
One Pot

Background: Pyranopyrazoles have a variety of biological activities and can be obtained by various starting materials and synthetic methods. Also, pyrazolopyrano[2,3-b]quinolins that contain pyranopyrazole moiety, have some biological activities such as anti acetylcholinesterase, anti butyrylcholinesterase activity. In this research, our objective is to prepare pyranopyrazole compounds and pyrazolopyrano[2,3-b]quinolins in a simple way and then evaluate their antibacterial effect. Methods: In this study, pyrano[2,3-c]pyrazole derivatives have been synthesized by condensing malononitrile, aromatic aldehydes, and 3-methyl-1-phenyl-2-pyrazolin-5-one in the presence of magnesium perchlorate as a catalyst. Then we prepared pyrazolopyrano[2,3-b]quinolins via subsequent Friedlander reaction between cyclohexanone and the obtained pyrano[2,3-c]pyrazoles. Also, the antimicrobial activity of the synthesized pyrazolopyrano[2,3-b]quinolins against Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli were measured. Then we studied molecular docking of them to find the predicted compounds' interactions and binding energy with DNA-gyrase with the AutoDock 4.2 software. Results: Pyrazolopyrano[2,3-b]quinolins were synthesized in optimized conditions. Evaluation of their antibacterial activities showed that these compounds have moderate to good antibacterial activities against four bacteria species. Also molecular docking tests of docked compounds showed a strong bonding interaction with DNA-Gyrase and had been docked into the intercalation place of DNA of DNA-gyrase complex. The molecule bounded to the DNA stabilized by the H bonds, hydrophobic interactions, and π-π interaction. Conclusion: We have developed an efficient and one-pot ecofriendly protocol for the synthesis of some novel pyrano[2,3-c]pyrazol derivatives and pyrazolopyrano[2,3-b]quinolins under simple conditions and then tested them for their antibacterial activities. Also, we studied molecular docking of them. These compounds showed moderate to good inhibitory action.

scholarly journals Potential COVID-19 Drug Candidates Based on Diazinyl-Thiazol-Imine Moieties: Synthesis and Greener Pastures Biological Study

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 488
Author(s):  
Sraa Abu-Melha ◽  
Mastoura Mohamed Edrees ◽  
Musa A. Said ◽  
Sayed M. Riyadh ◽  
Nadia S. Al-Kaff ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Hydrophobic Interactions ◽  
Biological Activities ◽  
Aromatic Aldehydes ◽  
Docking Study ◽  
Biological Study ◽  
Spectroscopic Techniques ◽  
Drug Candidates ◽  
Before And After ◽  
Approved Drugs

A novel series of 1-aryl-N-[4-phenyl-5-(arylazo)thiazol-2-yl)methanimines has been synthesized via the condensation of 2-amino-4-phenyl-5-arylazothiazole with various aromatic aldehydes. The synthesized imines were characterized by spectroscopic techniques, namely 1H and 13C NMR, FTIR, MS, and Elemental Analysis. A molecular comparative docking study for 3a–f was calculated, with reference to two approved drugs, Molnupiravir and Remdesivir, using 7BQY (Mpro; PDB code 7BQY; resolution: 1.7 A°) under identical conditions. The binding scores against 7BQY were in the range of −7.7 to −8.7 kcal/mol for 3a–f. The high scores of the compounds indicated an enhanced binding affinity of the molecules to the receptor. This is due to the hydrophobic interactions and multi-hydrogen bonds between 3a–f ligands and the receptor’s active amino acid residues. The main aim of using in silco molecular docking was to rank 3a–f with respect to the approved drugs, Molnupiravir and Remdesivir, using free energy methods as greener pastures. A further interesting comparison presented the laydown of the ligands before and after molecular docking. These results and other supporting statistical analyses suggested that ligands 3a–f deserve further investigation in the context of potential therapeutic agents for COVID-19. Free-cost, PASS, SwissADME, and Way2drug were used in this research paper to determine the possible biological activities and cytotoxicity of 3a–f.

scholarly journals Thiazolo-Pyrimidine Analogues: Synthesis, Characterization and Docking Studies Guided Antimicrobial Activities

2020 ◽  
Vol 11 (2) ◽  
pp. 9443-9455
Keyword(s):  
Aromatic Aldehydes ◽  
Dna Gyrase ◽  
Docking Study ◽  
Antimicrobial Activities ◽  
Docking Studies ◽  
One Pot ◽  
Standard Drug ◽  
Toluene Sulfonic Acid ◽  
Pyrimidine Analogues

In the current study, bicyclic 1-(7-methyl-3,5-diphenyl-5H-thiazolo(3,2-α)pyrimidine-6-yl)ethanone (4a-l) derivatives have been designed and conveniently synthesized by one-pot three-component method via cyclocondensation of substituted 4-phenylthiazole-2-amine (1a-c), acetylacetone (2) and various aromatic aldehydes (3a-d) in the presence of p-toluene sulfonic acid (PTSA) under acetonitrile solvent medium. The synthesized compounds (4a-l) have been characterized by spectral analysis and subjected to docking study against protein DNA gyrase (PDB Code: 1KZN), and also, the compounds were screened for their in vitro antimicrobial activities. The bioassay of the synthesized compounds envisioned that the compound 4k emerged as a broad-spectrum antibacterial agent, and 4l emerged as a good antifungal agent compared to standard drug.

Design, in silico Analysis, Synthesis and Evaluation of Novel Benzofused Nitrogen Containing Heterocyclic N-Substituted Mercaptobenzimidazole Derivatives as Potential Antimicrobial Agent

2021 ◽  
Vol 6 (2) ◽  
pp. 121-127
Author(s):  
Tejaswini D. Patil ◽  
Sunil V. Amrutkar ◽  
Amol S. Jagdale
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Candida Albicans ◽  
Molecular Docking ◽  
In Silico Analysis ◽  
Dna Gyrase ◽  
Docking Study ◽  
Benzimidazole Derivatives ◽  
Heterocyclic Derivatives ◽  
Subunit B

Benzimidazole containing mercapto group at the 2nd position is attractive nucleus for the modification with wider pharmacological activities. The aim of this study is to design benzofused nitrogen containing heterocyclic derivatives of mercapto benzimidazole using molecular docking. Using an effective procedure, N-substituted mercapto benzimidazole derivatives was synthesized. The antimicrobial activity of all the synthesized compounds was tested against four different organisms viz. E. coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Molecular docking of mercapto benzimidazole derivatives against DNA gyrase subunit B PDB: 5l3j and Staphylococcus aureus tyrosyltRNA synthetase PDB:1jij was performed using docking protocol. The compound binds to the active site of DNA gyrase subunit B (1KZN) in a docking study, indicating that it may have antimicrobial activity. Compounds MB3 and MB5 have good antimicrobial capacity whereas compound MB4 has the high activity against Candida albicans.

Synthesis, Antiproliferative Activity and Molecular Docking of New Thiazole/Benzothiazole Fused Pyranopyrimidine Derivatives

2020 ◽  
Vol 17 (12) ◽  
pp. 951-958
Author(s):  
Pallava Nagaraju ◽  
Pedavenkatagari Narayana Reddy ◽  
Pannala Padmaja ◽  
Vinod G. Ugale
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Antiproliferative Activity ◽  
Aromatic Aldehydes ◽  
Human Colon ◽  
Docking Studies ◽  
Human Colon Cancer ◽  
One Pot ◽  
Human Embryonic Kidney Cells ◽  
Heterocyclic Molecules

A new class of 4H,5H-benzo[4,5]thiazolo[3,2-a]pyrano[2,3-d]pyrimidin-5-one and 5H,6Hpyrano[ 2,3-d]thiazolo[3,2-a]pyrimidin-5-one derivatives were synthesized via the one-pot threecomponent reaction of 2-hydroxy-4H-benzo[4,5]thiazolo[3,2-a]pyrimidin-4-one and 7-hydroxy-5Hthiazolo[ 3,2-a]pyrimidin-5-one to various aromatic aldehydes and malononitrile. This domino transformation involves the formation of pyranopyrimidine ring by the formation of three C–C bonds and one C– O bond a single synthetic operation. As the products precipitate out of the reaction, simple filtration is enough to gather the products, and thus, there is no need for work-up or column-chromatography. The synthesized thiazole/benzothiazole fused pyranopyrimidine derivatives were evaluated for their antiproliferative activity against four cancer cell lines namely DU 145 (prostate cancer), Hela (Human cervical cancer), MDA-MB-231 (breast cancer), HT-29 (Human colon cancer) and normal cell line HEK293 (human embryonic kidney cells). The results demonstrated that synthesized compounds were selective in its cytotoxicity to cancer cells compared to normal cells. Among these compounds, 2-amino-9- methoxy-5-oxo-4-(3,4,5-trimethoxyphenyl)-4H,5H-benzo[4,5]thiazolo[3,2-a]pyrano[2,3-d]pyrimidine- 3-carbonitrile 4i exhibited the most potent antiproliferative activity against the tested cell lines. Molecular docking studies revealed that these active heterocyclic molecules bind selectively in the colchicine binding site of tubulin polymer.

Synthesis, Antimicrobial Evaluation and Docking Study of Novel Thiosemicarbazone clubbed with 1,2,3-Triazoles

2020 ◽  
Vol 16 ◽  
Author(s):  
Adinath D. Badar ◽  
Shubham M. Sulakhe ◽  
Mahesh B. Muluk ◽  
Naziya N. M. A. Rehman ◽  
Prashant P. Dixit ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Biological Activities ◽  
Dna Gyrase ◽  
Docking Study ◽  
Antimicrobial Activities ◽  
Diffusion Method ◽  
Molecular Docking Study ◽  
Triazole Derivatives ◽  
Antibacterial And Antifungal

Background: Thiosemicarbazone, 1,2,3-triazole and their derivatives received great pharmaceutical importance due to their prominent biological activities. In the present study, the molecular hybrid thiosemicarbazone-1,2,3-triazoles derivatives were synthesized and screened for their antimicrobial activities. Methods: A series of thiosemicarbazone clubbed with 1,2,3-triazole derivatives were synthesized via click chemistry approach in good yields. The structures of synthesized compounds were assigned by their spectral data. The in vitro antimicrobial activity was performed by the agar well diffusion method. A molecular docking study was performed to identify the possible mode of action of synthesized derivatives. Results: The compounds 5d, 5h, 5i and 5k have exhibited excellent antimicrobial activities against both antibacterial and antifungal pathogens. The active thiosemicarbazone-1,2,3-triazole derivatives have shown excellent binding affinity towards DNA gyrase. Conclusion: The molecular hybrid thiosemicarbazone-1,2,3-triazole derivatives were synthesized. The newly synthesized compounds were evaluated for their antimicrobial activities. Few of the thiosemicarbazone-1,2,3-triazoles derivatives have exhibited good antimicrobial activities. They have been shown excellent binding affinity towards DNA gyrase.

Quantitative structure-activity relationship model, molecular docking simulation and computational design of some novel compounds against DNA gyrase receptor.

2020 ◽  
Vol 16 ◽  
Author(s):  
Shola Elijah Adeniji
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Binding Energy ◽  
Biological Activities ◽  
Docking Simulation ◽  
Dna Gyrase ◽  
Computational Design ◽  
Multi Drug Resistance ◽  
Drug Candidate ◽  
Standard Drug

Introduction: Mycobacterium tuberculosis has instigated a serious challenge toward the effective treatment of tuberculosis. The reoccurrence of the resistant strains of the disease to accessible drugs/medications has mandate for the development of more effective anti-tubercular agents with efficient activities. Time expended and costs in discovering and synthesizing new hypothetical drugs with improved biological activity have been a major challenge toward the treatment of multi-drug resistance strain M. tuberculosis (TB). Meanwhile, to solve the problem stated, a new approach i.e. QSAR which establish connection between novel drugs with a better biological against M. tuberculosis is adopted. Methods: The anti-tubercular model established in this study to forecast the biological activities of some anti-tubercular compounds selected and to design new hypothetical drugs is subjective to the molecular descriptors; MATS7s, SM1_DzZ, SpMin4_Bhv, TDB3v and RDF70v. Ligand-receptor interactions between quinoline derivatives and the receptor (DNA gyrase) was carried out using molecular docking technique by employing the PyRx virtual screening software and discovery studio visualizer software. Furthermore, docking study indicates that compounds 20 of the derivatives with promising biological activity have the utmost binding energy of -17.79 kcal/mol. Results: Meanwhile, the interaction of the standard drug; isoniazid with the target enzyme was observed with the binding energy -14.6 kcal/mol which was significantly lesser than the binding energy of the ligand (compound 20).Therefore, compound 20 served as a template structure to designed compounds with more efficient activities. Among the compounds designed; compounds 20p was observed with better anti-tubercular activities with more prominent binding affinities of -24.3kcal/mol. Conclusion: The presumption of this research aid the medicinal chemists and pharmacist to design and synthesis a novel drug candidate against the tuberculosis. Moreover, in-vitro and in-vivo test could be carried out to validate the computational results.

scholarly journals Synthesis, characterisation and antibacterial evaluation of some novel 1-phenyl-1h-tetrazole-5-thiol derivatives

2019 ◽  
Vol 10 (2) ◽  
pp. 1136-1142
Author(s):  
Athraa H Mekky ◽  
Sajida M Thamir
Keyword(s):  
Staphylococcus Aureus ◽  
Biological Activities ◽  
Aromatic Aldehydes ◽  
Maximum Activity ◽  
Phenacyl Bromide ◽  
Alkylation Reaction ◽  
E Coli ◽  
Percentage Yield ◽  
And Staphylococcus Aureus ◽  
Antibacterial Evaluation

The aim of the study is to synthesise and. Characterize — some novel, "tetrazole., -5-thiol” derivatives. Firstly, the “1-phenyl-1H7-tetrazole-5-thiol” (A1) has been., synthesised by the reaction of phenylisothiocyanate with NaN3 in water as a solvent. Secondly, the tetrazole-5-thiol derivatives (A2-A4) were synthesised by the alkylation reaction of the compound (A1) with chloroacetone, phenacyl bromide and chloromethyl acetate respectively. The resulted percentage yield was relatively high (92%, %95, %90 respectively). Compound (A5) was synthesised by the reaction of ethyl acetate tetrazole derivative (A4) with hydrazine. Moreover, the derivatives (A6-A11) were synthesised by the reaction of the (A5) with various substituted aromatic aldehydes. Moreover, compounds (A12-A13) have been synthesised by the cyclization reaction of compound A5 with acetylacetone and phenyl acetylacetone respectively. The produced compounds have been identified by IR, 13C-NMR and 1H-NMR Spectroscopy, and the quantities of various of the physical data (melting point, the shape of crystal and color). Finally, the compounds were examined for their biological activities alongside two kinds of bacteria (E. Coli and Staphylococcus aureus). Compounds A2, A4, A8, A11 and A13 showed the highest inhibition activity against E. Coli. Compounds A2, A9, A10and A13 showed the maximum activity against Staphylococcus aureus.

Sign in / Sign up

Export Citation Format

Share Document