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.

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 New Mononuclear and Binuclear Cu(II), Co(II), Ni(II), and Zn(II) Thiosemicarbazone Complexes with Potential Biological Activity: Antimicrobial and Molecular Docking Study

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2288
Author(s):  
Ahmed Gaber ◽  
Moamen S. Refat ◽  
Arafa A.M. Belal ◽  
Ibrahim M. El-Deen ◽  
Nader Hassan ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Biological Activity ◽  
Molecular Docking ◽  
Metal Complexes ◽  
Analytical Data ◽  
Docking Study ◽  
Spectroscopic Techniques ◽  
Molecular Docking Study ◽  
Tetrahedral Geometry ◽  
Thiosemicarbazone Complexes

Herein, we report the synthesis of eight new mononuclear and binuclear Co2+, Ni2+, Cu2+, and Zn2+ methoxy thiosemicarbazone (MTSC) complexes aiming at obtaining thiosemicarbazone complex with potent biological activity. The structure of the MTSC ligand and its metal complexes was fully characterized by elemental analysis, spectroscopic techniques (NMR, FTIR, UV-Vis), molar conductivity, thermogravimetric analysis (TG), and thermal differential analysis (DrTGA). The spectral and analytical data revealed that the obtained thiosemicarbazone-metal complexes have octahedral geometry around the metal center, except for the Zn2+-thiosemicarbazone complexes, which showed a tetrahedral geometry. The antibacterial and antifungal activities of the MTSC ligand and its (Co2+, Ni2+, Cu2+, and Zn2+) metal complexes were also investigated. Interestingly, the antibacterial activity of MTSC- metal complexes against examined bacteria was higher than that of the MTSC alone, which indicates that metal complexation improved the antibacterial activity of the parent ligand. Among different metal complexes, the MTSC- mono- and binuclear Cu2+ complexes showed significant antibacterial activity against Bacillus subtilis and Proteus vulgaris, better than that of the standard gentamycin drug. The in silico molecular docking study has revealed that the MTSC ligand could be a potential inhibitor for the oxidoreductase protein.

Selection of oxypeucedanin as a potential antagonist from molecular docking analysis of HSP90

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Joshua Oluwasegun Bamidele ◽  
George Oche Ambrose ◽  
Oluwaseun Suleiman Alakanse
Keyword(s):  
Molecular Docking ◽  
Liver Toxicity ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Computational Docking ◽  
Drug Candidates ◽  
Expression Rate ◽  
Client Proteins

AbstractHSP90 is observed as one of the copious molecular chaperones that play a key role in mediating appropriate folding, maturation, and firmness of many client proteins in cells. The expression rate of HSP90 in cancer cells is at a level of 2- to 10-fold higher than the 1- to 2-fold of its unstressed and healthy ones. To combat this, several inhibitors to HSP90 protein have been studied (such as geldanamycin and its derivative 17-AAG and 17-DMAG) and have shown some primary side effects including plague, nausea, vomiting, and liver toxicity, hence the search for the best-in-class inhibitor for this protein through in silico. This study is aimed at analyzing the inhibitory potency of oxypeucedanin-a furocoumarin derivations, which have been reported to have antipoliferative activity in human prostrate carcinoma DN145 cells, and three other drug candidates retrieved from the literature via computational docking studies. The results showed oxypeucedanin as the compound with the highest binding energy of −9.2 kcal/mol. The molecular docking study was carried out using PyRx, Auto Dock Vina option, and the target was validated to confirm the proper target and the docking procedure employed for this study.

scholarly journals Synthesis, characterization (IR, 1H, 13C & 31P NMR), fungicidal, herbicidal and molecular docking evaluation of steroid phosphorus compounds

2019 ◽  
Vol 17 (1) ◽  
pp. 621-628 ◽  
Author(s):  
Mahboob Alam ◽  
Youngwon Kim ◽  
Soonheum Park
Keyword(s):  
Molecular Docking ◽  
Binding Free Energy ◽  
Docking Study ◽  
Herbicidal Activity ◽  
Phosphorus Compounds ◽  
Moderate Activity ◽  
Spectroscopic Techniques ◽  
Molecular Docking Study ◽  
Mycelium Growth ◽  
Phosphorus Containing

AbstractPhosphorus containing steroidal derivatives such as 3β-oxo-[diazaphosphalidine-2’-one] stigmast-5-ene and 3β-oxo-[diazaphosphalidine-2’-one] stigmast-5,22-diene were designed, synthesized and characterized using spectroscopic techniques (IR, 1H, 13C & 31P NMR, HRMS) and elemental analysis. The fungicidal and herbicidal studies of the compounds were performed and the experimental outcomes showed that compound 4 showed a good fungicidal activity against mycelium growth of fungi, while in the case of herbicidal activity, both compounds show a moderate activity compared to the commercial drug; Atrazine. The binding free energy of active compound 4 to the receptor named 4-Hydroxyphenylpyruvate dioxygenase (HPPD) was calculated using the molecular docking study. The HPPD is one of the most effective targets of plants for the herbicide study.

scholarly journals Identification of Compounds from Nigella Sativa as New Potential Inhibitors of 2019 Novel Coronasvirus (Covid-19): Molecular Docking Study.

2020 ◽  
Author(s):  
Salim Bouchentouf ◽  
Noureddine Missoum
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Nigella Sativa ◽  
Specific Treatment ◽  
Docking Study ◽  
Clinical Test ◽  
Molecular Docking Study ◽  
Great Opportunity ◽  
Drug Candidates ◽  
Energy Score

<p>The spread of the global COVID-19 pandemic, the lack of specific treatment and the urgent situation requires use of all resources to remedy this scourge. In the present study, using molecular docking, we identify new probable inhibitors of COVID-19 by molecules from <i>Nigella sativa L</i>, which is highly reputed healing herb in North African societies and both Islamic and Christian traditions. The discovery of the M<sup>pro</sup> protease structure in COVID-19 provides a great opportunity to identify potential drug candidates for treatment. Focusing on the main proteases in CoVs (3CL<sup>pro</sup>/M<sup>pro</sup>) (PDB ID 6LU7 and 2GTB); docking of compounds from <i>Nigella Sativa</i> and drugs under clinical test was performed using Molecular Operating Environment software (MOE). Nigelledine docked into 6LU7 active site gives energy complex about -6.29734373 Kcal/mol which is close to the energy score given by chloroquine (-6.2930522 Kcal/mol) and better than energy score given by hydroxychloroquine (-5.57386112 Kcal/mol) and favipiravir (-4.23310471 kcal/mol). Docking into 2GTB active site showed that α- Hederin gives energy score about-6.50204802 kcal/mol whcih is better energy score given by chloroquine (-6.20844936 kcal/mol), hydroxychloroquine (-5.51465893 kcal/mol)) and favipiravir (-4.12183571kcal/mol). Nigellidine and α- Hederin appeared to have the best potential to act as COVID-19 treatment. Further, researches are necessary to testify medicinal use of identified and to encourage preventive use of <i>Nigella Sativa </i>against coronavirus infection.</p>

scholarly journals Identification of Bioactive Phytoconstituents from the Plant Euphorbia hirta as Potential Inhibitor of SARS-CoV-2: an In-Silico Approach

2021 ◽  
Vol 12 (2) ◽  
pp. 1385-1396
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Biological Activities ◽  
Specific Treatment ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Standard Drug ◽  
Euphorbia Hirta ◽  
Main Protease

Currently, the entire globe is under the deadliest pandemic of Covid-19 caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). At present, no specific treatment is available to combat COVID-19 infection. Euphorbia hirta (Euphorbiaceae) have been reported for a variety of biological activities, including antiviral. The present investigation aimed to identify potential phytoconstituents of the plant E. hirta from the category flavonoids and coumarins against the SARS-CoV-2 using in silico approach. The molecular docking studies were performed using two different targets of SARS-CoV-2, namely Main protease (Mpro; PDB ID: 6M2N) and RNA-dependent RNA polymerase (RdRp; PDB ID: 7BW4). Based on the molecular docking study in comparison with standard drug, four compounds, namely Euphrobianin, Quercetin, 3-o-alpha-rhamnoside, Isoquercitrin, and rutin, were screened against the target Mpro. Three phytoconstituents, euphorbianin, myricetin, and rutin, were screened against the target RdRp. In the in silico toxicity studies of screened phytoconstituents, except myrectin all were predicted safe. Results of euphorbianin and rutin were found more interesting as both compounds had high binding affinity against both targets. Finally, we want to conclude that euphrobianin, quercetin 3-o-alpha-rhamnoside, isoquercitrin, and rutin could be further explored rapidly as they may have the potential to fight against COVID-19.

scholarly journals Design, Synthesis, Molecular Docking, and Kinetic Study of 3-Amino-2,4-Diarylbenzo[4,5]Imidazo[1,2-a]Pyrimidines as Novel, Potent Α-Glucosidase Inhibitor

2021 ◽  
Author(s):  
Fariba Peytam ◽  
Ghazaleh Takalloobanafshi ◽  
Toktam Saadattalab ◽  
Zahra Emamgholipour ◽  
Maryam Norouzbahari ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Kinetic Study ◽  
Docking Study ◽  
Type Ii Diabetes Mellitus ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Drug Candidates ◽  
Glucosidase Inhibitors

Abstract In an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a-ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their α-glucosidase inhibitory activities were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which may provide new drug candidates in the treatment of type II diabetes mellitus. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against α-glucosidase (IC50 = 16.4 ± 0.36 μM) which was 45.7 times more potent than acarbose as standard inhibitor (IC50 = 750.0 ± 1.5 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.

In Vitro Antioxidant, Antimicrobial and Molecular Docking Studies of Fosphenytoin and Regadenoson Impurities

2020 ◽  
Vol 8 (1) ◽  
pp. 63-69
Author(s):  
S. Sathiyanarayanan ◽  
◽  
C.S. Venkatesan ◽  
S. Kabilan ◽  
◽  
...  
Keyword(s):  
Molecular Docking ◽  
Drug Product ◽  
Active Pharmaceutical Ingredient ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Gaba A ◽  
Pharmacokinetic Properties ◽  
Approved Drugs

Regadenoson and Fosphenytoin are USFDA approved drugs which is used for coronary vasodilator and convulsive status epileptics respectively. It is quite natural that low levels of reagents or side products are present in the final active pharmaceutical ingredient (API) or drug product as impurities. Such impurities may have unwanted toxicities, including genotoxicity and carcinogenicity. Hence, it is important to study on impurities present in both the drugs. There are 9 impurities were identified from both drugs and studied pharmacokinetic properties using Qikprop module from Schrödinger software. From the 9 compounds of both the drug’s impurities, 5 compounds obey the Lipinski rule of five and the remaining compounds are having 1 to 3 penalties. All the compounds were subjected to molecular docking study with thermo stabilised HUMAN A2A Receptor with adenosine bound protein (PDB ID: 2YDO) for regadenoson impurities and fosphenytoin impurities were docked with Human GABA-A receptor alpha1-beta2-gamma2 subtype in complex with GABA and flumazenil, conformation A protein (PDB id: 6D6U). All the compounds are showed very good interaction with docked proteins. Further selected compound subjected to in vitro Antibacterial (Gram positive, Gram negative), Antifungal and Antioxidant (DPPH and FRAP) studies.

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