Synthesis, Docking Study and Biological Activities Evaluation of 1‐Amidoalkyl‐2‐naphthol Derivatives as Dual Inhibitors of Cholinesterase and α‐Glucosidase

2020 ◽  
Vol 5 (19) ◽  
pp. 5515-5520 ◽  
Author(s):  
Khawla Boudebbous ◽  
Houssem Boulebd ◽  
Chawki Bensouici ◽  
Dominique Harakat ◽  
Raouf Boulcina ◽  
...  
Keyword(s):  
Biological Activities ◽  
Docking Study ◽  
Dual Inhibitors ◽  
Naphthol Derivatives

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.

Synthesis, Biological Evaluation and Molecular Docking Study of Cyclic Diarylheptanoids as Potential Anticancer Therapeutics

2020 ◽  
Vol 20 (4) ◽  
pp. 464-475 ◽  
Author(s):  
Yang Lu ◽  
Wencui Yin ◽  
Mohammad S. Alam ◽  
Adnan A. Kadi ◽  
Yurngdong Jahng ◽  
...  
Keyword(s):  
Anticancer Drugs ◽  
In Silico ◽  
Topoisomerase I ◽  
Biological Activities ◽  
Cancer Cell Line ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Topoisomerase Iiα ◽  
Inhibitory Activities ◽  
Formed Hydrogen

Background: Cancer is one of the leading causes of mortality globally. To cope with cancer, it is necessary to develop anticancer drugs. Bioactive natural products, i.e. diarylheptanoids, have gained significant attention of researchers owing to their intriguing structures and potent biological activities. In this article, considering the development of anticancer drugs with enhanced selectivity towards cancerous cells, a series of Cyclic Diarylheptanoids (CDHs) are designed, synthesized and evaluated their biological activity. Objective: To establish an easy route for the synthesis of diarylheptanoids, and evaluate their antiproliferative, and topoisomerase-I & -IIα inhibitory activities, for developing potential anticancer drugs among CDHs. Methods: Diarylheptanoids were synthesized from reported linear diarylheptanoids using the classical Ullmann reaction. Antibacterial activity was evaluated by the filter paper disc diffusion method. Cell viability was assessed by measuring mitochondrial dehydrogenase activity with a Cell Counting Kit (CCK-8). Topoisomerases I and II (topo-I and -IIα) inhibitory activity was measured by the assessment of relaxation of supercoiled pBR322 plasmid DNA. IFD protocol of Schrodinger Maestro v11.1 was used to characterize the binding pattern of studied compounds with the ATPase domain of the human topo-IIα. Results: The synthesized CDHs were evaluated for their biological activities (antibacterial, antiproliferative, and topoisomerase-I & -IIα inhibitory activities, respectively). Leading to obtain a series of anticancer agents with the least inhibitory activities against different microbes, improving their selectivity for cancer cells. In brief, most of the synthesized CDHs had excellent antiproliferative activity against T47D (human breast cancer cell line). Pterocarine possessed the strongest activity (2i; IC50 = 0.63µM) against T47D. The cyclic diarylheptanoid 2b induced 30% inhibition of topoisomerase-IIα activity at 100μM compared with the reference of etoposide, which induced 72% inhibition. Among the tested compounds, galeon (2h) displayed very low activity against four bacterial strains. Compounds 2b, 2h, and 2i formed hydrogen bonds with Thr215, Asn91, Asn120, Ala167, Lys168 and Ile141 residues, which are important for binding of ligand compound to the ATPase binding site of topoisomerase IIα by acting as ATP competitive molecule validated by docking study. In silico Absorption, Distribution, Metabolism and Excretion (ADME) analysis revealed the predicted ADME parameters of the studied compounds which showed recommended values. Conclusion: A series of CDHs were synthesized and evaluated for their antibacterial, antiproliferative, and topo-I & -IIα inhibitory activities. SARs study, molecular docking study and in silico ADME analysis were conducted. Five compounds exhibited excellent and selective antiproliferative activity against the human breast cancer cell line (T47D). Among them, a compound 2h showed topo-IIα activity by 30% at 100µM, which represented a moderate intensity of inhibition compared with etoposide. Three of them formed hydrogen bonds with Thr215, Asn91, Asn120, and Ala167 residues, which are considered as crucial residues for binding to the ATPase domain of topoisomerase IIα. According to in silico drug-likeness property analysis, three compounds are expected to show superiority over etoposide in case of absorption, distribution, metabolism and excretion.

scholarly journals New Benzoxazole Derivatives as Antiprotozoal Agents: In Silico Studies, Synthesis, and Biological Evaluation

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Mohamed A. Abdelgawad ◽  
Mohammad M. Al-Sanea ◽  
Mohamed A. Zaki ◽  
Enas I. A. Mohamed ◽  
Shabana I. Khan ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Antimalarial Activity ◽  
Biological Activities ◽  
Docking Study ◽  
Antimicrobial Activities ◽  
Biological Evaluation ◽  
Molecular Docking Study ◽  
Chromatographic Separations ◽  
Major Mechanism ◽  
In Silico Studies

Background. Benzoxazole derivatives have different biological activities. In pursuit of designing novel chemical entities with antiprotozoal and antimicrobial activities, benzoxazolyl aniline was utilized as a privileged scaffold of a series of (3-benzoxazole-2-yl) phenylamine derivatives, 3-benzoxazoloyl acetamide, and butyramide derivatives. Methods. These novel analogs were synthesized in straightforward simple chemistry without any quantitative chromatographic separations in reasonable yields. The biological evaluation of all target compounds as potential antimalarial, antileishmanial, antitrypanosomal, and antimicrobial agents was performed by various well-established cell-based methods. Results. Compounds 6d and 5a showed promising biological screening data. The amidation of 3-benzoxazolyl aniline 1 with the chloroacetyl functional group resulted in a good antimalarial activity and showed moderate inhibitory activities against leishmanial and trypanosomal spp. Moreover, chloroacetyl functionalization of benzoxazolyl aniline serves as a good early goal for constructing and synthesizing new antimicrobial and antiprotozoal agents. The molecular docking study rationalizes the relative inhibitory activity of compound 5a as an antimalarial agent with the deregulation of PfPNP activity which has emerged as a major mechanism of these targets.

Novel 1,2-thiazine-pyridine hybrid: Design, synthesis, antioxidant activity and molecular docking study

2022 ◽  
Vol 19 ◽  
Author(s):  
Rania B. Bakr ◽  
Nadia A.A. Elkanzi
Keyword(s):  
Antioxidant Activity ◽  
Ascorbic Acid ◽  
Biological Activities ◽  
Radical Scavenging ◽  
Reducing Power ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Sod Activity ◽  
Design Synthesis ◽  
In Silico Docking

Background & objectives: 1,2-thiazine and pyridine heterocycles drew much attention due to their biological activities including antioxidant activity. Based upon fragment based drug design, novel pyrido[1,2]thiazines 9a-c, thiazolidinopyrido[1,2]thiazines 10a-c and azetidinopyrido[1,2]thiazines 11a-c were designed and prepared. Methods: These novel derivatives 9a-c, 10a-c and 11a-c were subjected to screening for their antioxidant activity via various assays as DPPH radical scavenging potential, reducing power assay and metal chelating potential. Results: All the assayed derivatives exhibited excellent antioxidant potential and the tested compounds 9a, 9b, 10a, 10b, 11a and 11b exhibited higher DPPH scavenging potential (EC50 = 32.7, 53, 36.1, 60, 40.6 and 67 µM, respectively) than ascorbic acid (EC50 = 86.58 µM). While targets 9a, 10a and 11a (RP50 = 52.19, 59.16 and 52.25 µM, respectively) exhibited better reducing power than the ascorbic acid (RP50 = 84.66 µM). Computational analysis had been utilized to prophesy the bioactivity and molecular properties of the target compounds. Conclusion: To predict the binding manner of the novel derivatives as antioxidants, in-silico docking study had been performed to all the newly prepared compounds inside superoxide dismutase (SOD) and catalase (CAT) active site. The most active antioxidant candidate 9a (EC50 = 32.7 µM, RP50 = 52.19 µM) displayed excellent binding with Lys134 amino acid residing at Cu-Zn loop of SOD with binding energy score = -7.54 Kcal/mol thereby increase SOD activity and decrease reactive oxygen species.

scholarly journals A New Tyrosinase Inhibitor from the Red Alga Symphyocladia latiuscula (Harvey) Yamada (Rhodomelaceae)

Marine Drugs ◽  
2019 ◽  
Vol 17 (5) ◽  
pp. 295 ◽  
Author(s):  
Pradeep Paudel ◽  
Aditi Wagle ◽  
Su Hui Seong ◽  
Hye Jin Park ◽  
Hyun Ah Jung ◽  
...  
Keyword(s):  
Methyl Ether ◽  
Inhibitory Activity ◽  
Biological Activities ◽  
Docking Study ◽  
Red Alga ◽  
Moderate Activity ◽  
Molecular Docking Study ◽  
Tyrosinase Inhibitory Activity ◽  
Ic50 Values ◽  
Catalytic Hydrogen

A marine red alga, Symphyocladia latiuscula (Harvey) Yamada (Rhodomelaceae), is a rich source of bromophenols with a wide array of biological activities. This study investigates the anti-tyrosinase activity of the alga. Moderate activity was demonstrated by the methanol extract of S. latiuscula, and subsequent column chromatography identified three bromophenols: 2,3,6-tribromo-4,5-dihydroxybenzyl methyl alcohol (1), 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (2), and bis-(2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether) (3). Bromophenols 1 and 3 exhibited potent competitive tyrosinase inhibitory activity against l-tyrosine substrates, with IC50 values of 10.78 ± 0.19 and 2.92 ± 0.04 μM, respectively. Against substrate l-3,4-dihydroxyphenylalanine (l-DOPA), compounds 1 and 3 demonstrated moderate activity, while 2 showed no observable effect. The experimental data were verified by a molecular docking study that found catalytic hydrogen and halogen interactions were responsible for the activity. In addition, compounds 1 and 3 exhibited dose-dependent inhibitory effects in melanin and intracellular tyrosinase levels in α-melanocyte-stimulating hormone (α-MSH)-induced B16F10 melanoma cells. Compounds 3 and 1 were the most effective tyrosinase inhibitors. In addition, increasing the bromine group number increased the mushroom tyrosinase inhibitory activity.

Regression Analysis and Docking Study of 4-Quinolylhydrazone Based Compounds as Antituberculosis Agents

2019 ◽  
Vol 4 (4) ◽  
pp. 248-255
Author(s):  
C.V. Bisen ◽  
M.R. Patle ◽  
R.M. Patle
Keyword(s):  
Regression Analysis ◽  
Model Building ◽  
Biological Activities ◽  
Docking Study ◽  
Biological Properties ◽  
Analysis Model ◽  
Docking Method ◽  
Building Purpose ◽  
Inhibition Studies ◽  
Molecular Docking Method

In present study, at the beginning, the molecules whose biological properties are known are well-thought-out as a known set for regression analysis model building purpose. Using the Datawarrior software the descriptors were calculated for known set. Novel substituted 4-hydrazinylqunoline molecules were designed, improved and their descriptors were calculated. Morever, the regression analysis model was used to determine the biological activities of these new molecules. Along with this, the inhibition studies for 1QPQ and 1KNC by molecular docking method were also carried out to validate the therapeutic nature of these molecules. Accordingly, it can be concluded that these moieties on further studies may evident to be therapeutic representative against Mycobacterium tuberculosis.

Novel N-substituted 5-aminosalicylamides as dual inhibitors of cyclooxygenase and 5-lipoxygenase enzymes: Synthesis, biological evaluation and docking study

2018 ◽  
Vol 78 ◽  
pp. 80-93 ◽  
Author(s):  
Mohamed K.S. El-Nagar ◽  
Hajjaj H.M. Abdu-Allah ◽  
Ola I.A. Salem ◽  
Abdel-Hamid N. Kafafy ◽  
Hanan S.M. Farghaly
Keyword(s):  
Docking Study ◽  
Biological Evaluation ◽  
Dual Inhibitors

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.

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