Synthesis and Molecular Docking Study of Novel COVID-19 Drug Candidates

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.

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

10.26434/chemrxiv.12055716.v1 ◽

2020 ◽

Cited By ~ 9

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

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 Nigella sativa L, which is highly reputed healing herb in North African societies and both Islamic and Christian traditions. The discovery of the Mpro protease structure in COVID-19 provides a great opportunity to identify potential drug candidates for treatment. Focusing on the main proteases in CoVs (3CLpro/Mpro) (PDB ID 6LU7 and 2GTB); docking of compounds from Nigella Sativa 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 Nigella Sativa against coronavirus infection.

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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

10.21203/rs.3.rs-144397/v1 ◽

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.

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

10.20944/preprints202004.0079.v1 ◽

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

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 Nigella sativa L, which is highly reputed healing herb in North African societies and both Islamic and Christian traditions. The discovery of the Mpro protease structure in COVID-19 provides a great opportunity to identify potential drug candidates for treatment. Focusing on the main proteases in CoVs (3CLpro/Mpro) (PDB ID 6LU7 and 2GTB); docking of compounds from Nigella Sativa 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 Nigella Sativa against coronavirus infection.

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Molecular Docking Study of Quercetein Analogues for Treating Tumours

International Journal of PharmTech Research ◽

10.20902/ijptr.2019.120405 ◽

2019 ◽

Vol 12 (4) ◽

pp. 30-34

Author(s):

S. Gejalakshmi ◽

N. Harikrishnan

Keyword(s):

Molecular Docking ◽

Drug Discovery ◽

Structural Diversity ◽

Docking Study ◽

Therapeutic Agents ◽

Drug Candidate ◽

Molecular Docking Study ◽

Drug Candidates ◽

Drug Compounds ◽

Scientific Task

Drug discovery leading to robust and viable lead candidate’s remains a challenging scientific task, which is the transition from a screening hit to a drug candidate, requires expertise and experience. Natural products and their derivatives have been recognized for many years as a source of therapeutic agents and of structural diversity. The present research attempts to describe the utilization of compounds derived from natural resources as drug candidates, with a focus on the success of these resources in the process of finding and discovering new and effective drug compounds, an approach commonly referred to as ―natural product drug discovery

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Spectroscopic Investigations, Computational Analysis and Molecular Docking to SAR-Cov-2 Targets Studies of 5,8-Quinolinedione Attached to Betulin Derivatives

Crystals ◽

10.3390/cryst11010076 ◽

2021 ◽

Vol 11 (1) ◽

pp. 76

Author(s):

Monika Kadela-Tomanek ◽

Maria Jastrzębska ◽

Krzysztof Marciniec ◽

Ewa Bębenek ◽

Elwira Chrobak ◽

...

Keyword(s):

Molecular Docking ◽

Electrostatic Potential ◽

Density Functional ◽

Molecular Electrostatic Potential ◽

Docking Study ◽

Molecular Docking Study ◽

Functional Theory ◽

Drug Candidates ◽

The Density Functional Theory ◽

Ft Ir

The 5,8-quinolinedione-betulin hybrids were investigated using spectroscopic methods as well as a variety of quantum chemical calculations in order to characterize their molecular structure. We used FT-IR and NMR spectroscopy supplemented by the density functional theory (DFT) calculations, molecular electrostatic potential (MEP) and molecular orbital (HOMO, LUMO) analyses. The experimental and calculated FT-IR spectra showed a good correlation for all compounds. Analysis of carbonyl band showed that the compounds are the 7-mono substituted. The calculated 1H NMR and 13C NMR spectra of hybrids reproduced well the experimental ones. Identification of C-6 and C-7 carbon atoms of 5,8-quinolinedione revealed the position of betulin moiety at the C-7 of 5,8-quinolinedione. Molecular electrostatic potential maps of hybrids allowed to recognize the electrophilic and nucleophilic regions within the molecules. The molecular docking study was used to examine the interaction between the 5,8-quinolinedione-betulin hybrids and the SARS-CoV-2 protein, like: Mpro and PLpro. The obtained results showed that compounds with the highest Dock Score are good anti-SARS-CoV-2 potential drug candidates.

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

10.26434/chemrxiv.12055716 ◽

2020 ◽

Cited By ~ 1

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

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 Nigella sativa L, which is highly reputed healing herb in North African societies and both Islamic and Christian traditions. The discovery of the Mpro protease structure in COVID-19 provides a great opportunity to identify potential drug candidates for treatment. Focusing on the main proteases in CoVs (3CLpro/Mpro) (PDB ID 6LU7 and 2GTB); docking of compounds from Nigella Sativa 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 Nigella Sativa against coronavirus infection.

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Synthesis, Molecular Docking Screening and Anti-Proliferative Potency Evaluation of Some New Imidazo[2,1-b]Thiazole Linked Thiadiazole Conjugates

Molecules ◽

10.3390/molecules25214997 ◽

2020 ◽

Vol 25 (21) ◽

pp. 4997

Author(s):

Huda R. M. Rashdan ◽

Aboubakr H. Abdelmonsef ◽

Ihsan A. Shehadi ◽

Sobhi M. Gomha ◽

Abdel Mohsen M. Soliman ◽

...

Keyword(s):

Molecular Docking ◽

Cell Lines ◽

Cancer Cell ◽

Docking Study ◽

Cancer Cell Lines ◽

Hepatic Cancer ◽

Molecular Docking Study ◽

Drug Candidates ◽

Ft Ir ◽

Thiadiazole Derivatives

Background: Imidazo[2,1-b]thiazole scaffolds were reported to possess various pharmaceutical activities. Results: The novel compound named methyl-2-(1-(3-methyl-6-(p-tolyl)imidazo[2,1-b]thiazol-2-yl)ethylidene)hydrazine-1-carbodithioate 3 acted as a predecessor molecule for the synthesis of new thiadiazole derivatives incorporating imidazo[2,1-b]thiazole moiety. The reaction of 3 with the appropriate hydrazonoyl halide derivatives 4a–j and 7–9 had produced the respective 1,3,4-thiadiazole derivatives 6a–j and 10–12. The chemical composition of all the newly synthesized derivatives were confirmed by their microanalytical and spectral data (FT-IR, mass spectrometry, 1H-NMR and 13C-NMR). All the produced novel compounds were screened for their anti-proliferative efficacy on hepatic cancer cell lines (HepG2). In addition, a computational molecular docking study was carried out to determine the ability of the synthesized thiadiazole molecules to interact with active site of the target Glypican-3 protein (GPC-3). Moreover, the physiochemical properties of the synthesized compounds were derived to determine the viability of the compounds as drug candidates for hepatic cancer. Conclusion: All the tested compounds had exhibited good anti-proliferative efficacy against hepatic cancer cell lines. In addition, the molecular docking results showed strong binding interactions of the synthesized compounds with the target GPC-3 protein with lower energy scores. Thus, such novel compounds may act as promising candidates as drugs against hepatocellular carcinoma.

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