scholarly journals Benzoquinoline Derivatives: A Straightforward and Efficient Route to Antibacterial and Antifungal Agents

2021 ◽  
Vol 14 (4) ◽  
pp. 335
Author(s):  
Vasilichia Antoci ◽  
Liliana Oniciuc ◽  
Dorina Amariucai-Mantu ◽  
Costel Moldoveanu ◽  
Violeta Mangalagiu ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Atp Synthase ◽  
In Silico ◽  
Cycloaddition Reaction ◽  
Biological Data ◽  
In Silico Admet ◽  
In Silico Studies ◽  
Topo Ii ◽  
Antibacterial And Antifungal ◽  
Best Fit

We report here the design, synthesis, experimental and in silico evaluation of the antibacterial and antifungal activity of some new benzo[f]quinoline derivatives. Two classes of benzo[f]quinolinium derivatives—(benzo[f]quinolinium salts (BQS) and pyrrolobenzo[f]quinolinium cycloadducts (PBQC)—were designed and obtained in two steps via a direct and facile procedure: quaternization followed by a cycloaddition reaction. The synthesized compounds were characterized by elemental and spectral analysis (FT-IR, 1H-NMR, 13C-NMR). The antimicrobial assay reveals that the BQS salts have an excellent quasi-nonselective antifungal activity against the fungus Candida albicans (some of them higher that the control drug nystatin) and very good antibacterial activity against the Gram positive bacterium Staphylococcus aureus. The PBQC compounds are inactive. Analysis of the biological data reveals interesting SAR correlations in the benzo[f]quinolinium series of compounds. The in silico studies furnished important data concerning the pharmacodynamics, pharmacokinetics and ADMET parameters of the BQS salts. Studies of the interaction of each BQS salt 3a–o with ATP synthase in the formed complex, reveal that salts 3j, 3i, and 3n have the best fit in a complex with ATP synthase. Study of the interaction of each BQS salt 3a-o with TOPO II in the formed complex reveals that salts 3j and 3n have the best-fit in complex with TOPO II. The in silico ADMET studies reveal that the BQS salts have excellent drug-like properties, including a low toxicity profile. Overall, the experimental and in silico studies indicate that compounds 3e and 3f (from the aliphatic series), respectively, and 3i, 3j and 3n (from the aromatic series), are promising leading drug candidates.

Copper-catalyzed Convenient Synthesis and SAR Studies of Substituted-1,2,3-triazole as Antimicrobial Agents

2018 ◽  
Vol 16 (1) ◽  
pp. 3-10
Author(s):  
Aniket P. Sarkate ◽  
Kshipra S. Karnik ◽  
Pravin S. Wakte ◽  
Ajinkya P. Sarkate ◽  
Ashwini V. Izankar ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antifungal Activity ◽  
Antimicrobial Agents ◽  
Cycloaddition Reaction ◽  
Dipolar Cycloaddition ◽  
One Pot ◽  
Triazole Derivatives ◽  
Sar Studies ◽  
Convenient Synthesis ◽  
Antibacterial And Antifungal

Background:A novel copper-catalyzed synthesis of substituted-1,2,3-triazole derivatives has been developed and performed by Huisgen 1,3-dipolar cycloaddition reaction of azides with alkynes. The reaction is one-pot multicomponent.Objective:We state the advancement and execution of a methodology allowing for the synthesis of some new substituted 1,2,3-triazole analogues with antimicrobial activity.Methods:A series of triazole derivatives was synthesized by Huisgen 1,3-dipolar cycloaddition reaction of azides with alkynes. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR, IR, MS and elemental analysis. All the synthesized compounds were tested for their antimicrobial activity against a series of strains of Bacillus subtilis, Staphylococcus aureus and Escherichia coli for antibacterial activity and against the strains of Candida albicans, Aspergillus flavus and Aspergillus nigar for antifungal activity, respectively.Results and Conclusion:From the antimicrobial data, it was observed that all the newly synthesized compounds showed good to moderate level of antibacterial and antifungal activity.

scholarly journals Antimicrobial Activity of Nitrogen-Containing 5-α-Androstane Derivatives: In Silico and Experimental Studies

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 224 ◽  
Author(s):  
Lela Amiranashvili ◽  
Nanuli Nadaraia ◽  
Maia Merlani ◽  
Charalampos Kamoutsis ◽  
Anthi Petrou ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antifungal Activity ◽  
In Silico ◽  
Web Applications ◽  
Experimental Studies ◽  
Docking Studies ◽  
Minimum Fungicidal Concentration ◽  
Antibacterial And Antifungal ◽  
Mic Minimum Inhibitory Concentration ◽  
Androstane Derivatives

We evaluated the antimicrobial activity of thirty-one nitrogen-containing 5-α-androstane derivatives in silico using computer program PASS (Prediction of Activity Spectra for Substances) and freely available PASS-based web applications (such as Way2Drug). Antibacterial activity was predicted for 27 out of 31 molecules; antifungal activity was predicted for 25 out of 31 compounds. The results of experiments, which we conducted to study the antimicrobial activity, are in agreement with the predictions. All compounds were found to be active with MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values in the range of 0.0005–0.6 mg/mL. The activity of all studied 5-α-androstane derivatives exceeded or was equal to those of Streptomycin and, except for the 3β-hydroxy-17α-aza-d-homo-5α-androstane-17-one, all molecules were more active than Ampicillin. Activity against the resistant strains of E. coli, P. aeruginosa, and methicillin-resistant Staphylococcus aureus was also shown in experiments. Antifungal activity was determined with MIC and MFC (Minimum Fungicidal Concentration) values varying from 0.007 to 0.6 mg/mL. Most of the compounds were found to be more potent than the reference drugs Bifonazole and Ketoconazole. According to the results of docking studies, the putative targets for antibacterial and antifungal activity are UDP-N-acetylenolpyruvoylglucosamine reductase and 14-α-demethylase, respectively. In silico assessments of the acute rodent toxicity and cytotoxicity obtained using GUSAR (General Unrestricted Structure-Activity Relationships) and CLC-Pred (Cell Line Cytotoxicity Predictor) web-services were low for the majority of compounds under study, which contributes to the chances for those compounds to advance in the development.

scholarly journals Synthesis, Structure-Activity Relationships (SAR) and in Silico Studies of Coumarin Derivatives with Antifungal Activity

2013 ◽  
Vol 14 (1) ◽  
pp. 1293-1309 ◽  
Author(s):  
Rodrigo de Araújo ◽  
Felipe Guerra ◽  
Edeltrudes de O. Lima ◽  
Carlos de Simone ◽  
Josean Tavares ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
In Silico ◽  
Coumarin Derivatives ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
In Silico Studies

Activity of Thiazine substituted 9-anilinoacridines against Corona virus (COVID19): An In-silico approach

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 482-490
Author(s):  
Kalirajan Rajagopal ◽  
Potlapati Varakumar ◽  
Baliwada Aparna ◽  
Vulsi Bodhya Sri ◽  
Gowramma Byran ◽  
...  
Keyword(s):  
In Silico ◽  
Binding Free Energy ◽  
Viral Disease ◽  
Docking Studies ◽  
Binding Modes ◽  
Main Protease ◽  
In Silico Admet ◽  
In Silico Studies ◽  
Life Threatening ◽  
Similar Mode

Coronavirus Disease 2019 (COVID-19), a life-threatening viral disease affected first in Wuhan, China, and quickly spread to more than 200 countries in the world in the year 2020. So many scientists are trying to discover novel drugs and vaccines for coronavirus and treatment for COVID-19. In the present article, in-silico studies have been performed to explore the binding modes of Thiazine substituted 9-anilinoacridines (1a-z) against SARS CoV 2 main protease (PDB id - 5R82) targeting the coronavirus using Schrodinger suit 2019-4. The molecular docking studies are performed by Glide module, in-silico ADMET screening was performed by Qik prop module, and the binding free energy of ligands was calculated using PRIME MM-GB/SA module of Schrodinger suite 2019-4, Maestro 21.2 version. From the in-silico results, Thiazine substituted 9-anilinoacridines like 1m, 1j, 1s and 1b are significantly active against SARS CoV 2 main protease with Glide score more than -5.4 when compared with the currently recommended drug for COVID19, Hydroxychloroquine (G score -5.47). The docking results of the Thiazine substituted 9-anilinoacridines exhibited similar mode of interactions with COVID19 and the residues GLN19, THR24, THR25, THR26, LEU27, HIE41, SER46, MET49, ASN142, GLN143, HIE164, MET165, ASP187, ARG188 and GLN189, play a crucial role in binding with ligands.

In Silico ADMET and Docking Studies of Thiazolidinedione-acetic-acid Hybrids as Antidiabetics with Cardioprotection

2020 ◽  
Vol 17 (12) ◽  
pp. 1475-1484
Author(s):  
Deepanwita Maji ◽  
Subir Samanta ◽  
Vaishali M. Patil
Keyword(s):  
Acetic Acid ◽  
Amino Acid ◽  
Side Effects ◽  
In Silico ◽  
Methyl Esters ◽  
Antioxidant Properties ◽  
Docking Studies ◽  
Single Amino Acid ◽  
In Silico Admet ◽  
In Silico Studies

Background: Type-2-diabetes mellitus is associated with many side effects affecting vital body organs, especially heart. Thiazolidinediones are potent antidiabetics. Studies have proven that amino-acids and peptides promote glucose transport, have antioxidant properties, and fewer side effects, thus we designed hybrids by combining amino-acid esters and peptide esters with 2, 4 thiazolidinedione acetic acid moiety which can act as antidiabetic agent with cardioprotection properties. Methodology: In vitro ADME, toxicity, and docking studies were performed using Qikprop3.1.OSIRIS, PROTOX (Prediction of Rodent Oral Toxicity), and FlexX 2.1.3, respectively. Results: All the designed molecules belong to three sub-series, i.e. 2, 4-dioxothiazolidine-5-acetic acid single amino acid hybrid methyl esters, 2, 4-dioxothiazolidine-5-acetic acid dipeptide hybrid methyl esters and 2, 4-dioxothiazolidine-5-acetic acid tripeptide hybrid methyl esters. All molecules were non-toxic. SSMA2, SSMA14, SSMA49, and SSDM50 showed good docking scores in 2PRG and 2UV4, respectively. Conclusion: The selected in silico studies helped to design hybrids with less toxicity, target specificity with dual activity as potential anti-diabetic and cardioprotective agents.

scholarly journals Activity of phytochemical constituents of Curcuma longa (turmeric) and Andrographis paniculata against coronavirus (COVID-19): an in silico approach

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Kalirajan Rajagopal ◽  
Potlapati Varakumar ◽  
Aparma Baliwada ◽  
Gowramma Byran
Keyword(s):  
Active Site ◽  
In Silico ◽  
Chemical Constituents ◽  
Curcuma Longa ◽  
Andrographis Paniculata ◽  
Significant Activity ◽  
Binding Modes ◽  
Main Protease ◽  
In Silico Admet ◽  
In Silico Studies

Abstract Background In early 2020, many scientists are rushing to discover novel drugs and vaccines against the coronavirus, and treatments for COVID-19, because coronavirus disease 2019 (COVID-19), a life-threatening viral disease, affected first in China and quickly spread throughout the world. In this article, in silico studies have been performed to explore the binding modes of chemical constituents for natural remedies like Curcuma longa (turmeric) and Andrographis paniculata against COVID-19 (PDB ID 5R82) targeting coronavirus using Schrodinger suit 2019-4. The molecular docking studies are performed by the Glide module, in silico ADMET screening was performed by the QikProp module, and binding energy of ligands was calculated using the Prime MM-GB/SA module. Results The chemical constituents from turmeric like cyclocurcumin and curcumin and from Andrographis paniculata like andrographolide and dihydroxy dimethoxy flavone are significantly binding with the active site of SARS CoV-2 main protease with Glide score more than − 6 when compared to the currently used drugs hydroxychloroquine (− 5.47) and nelfinavir (− 5.93). When compared to remdesivir (− 6.38), cyclocurcumin from turmeric is significantly more active. The docking results of the compounds exhibited similar mode of interactions with SARS CoV-2. Main protease and the residues THR24, THR25, THR26, LEU27, SER46, MET49, HIE41, GLN189, ARG188, ASP187, MET165, HIE164, PHE181, and THR54 play a crucial role in binding with ligands. Conclusion Based on in silico investigations, the chemical constituents from turmeric like cyclocurcumin and curcumin and from Andrographis paniculata like andrographolide and dihydroxy dimethoxy flavone, significantly binding with the active site of SARS CoV-2 main protease, may produce significant activity and be useful for further development.

Application of In silico Methods in the Design of Drugs for Neurodegenerative Diseases

2021 ◽  
Vol 21 ◽  
Author(s):  
Mohamad Haider ◽  
Anjali Chauhan ◽  
Sana Tariq ◽  
Dharam Pal Pathak ◽  
Nadeem Siddiqui ◽  
...  
Keyword(s):  
Drug Design ◽  
Neurodegenerative Diseases ◽  
In Silico ◽  
Brain Aging ◽  
Complex Nature ◽  
Computer Assisted ◽  
Complex Disorders ◽  
In Silico Admet ◽  
In Silico Studies ◽  
In Silico Methods

: Neurodegenerative diseases are complex disorders that cause neuron loss, brain aging and ultimately lead to death. These diseases are difficult to treat because of the complex nature of the nervous system and the available medicines are not able to heal them effectively. This fact implies the needs for novel therapeutics to be designed that are ready to stop or a minimum of retard the neurodegeneration process. These days, computer assisted drug design (CADD) approaches are a passage to extend the drug development efficiency and to reduce time and cost because traditional drug discovery is both time-consuming as well as costly. Computational or in silico methods came up with powerful tools in drug design against neurodegenerative diseases. This review presents the approaches and theoretical basis of CADD. Also, the successful applications of various in silico studies, including homology modeling, molecular docking, quantitative structure activity relationship (QSAR), molecular dynamic (MD), De Novo drug design, Pharmacophore-based drug design, Virtual Screening (VS), LIGPLOT Analysis, In silico ADMET and drug safety prediction, for treating neurodegenerative diseases have also been included in this review. Major emphasis is given to the Alzheimer’s disease and the Parkinson’s disease because these two are the most familiar neurodegenerative diseases.

scholarly journals A Novel Series of Acylhydrazones as Potential Anti-Candida Agents: Design, Synthesis, Biological Evaluation and In Silico Studies

Molecules ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 184 ◽  
Author(s):  
Anca-Maria Borcea ◽  
Gabriel Marc ◽  
Ioana Ionuț ◽  
Dan C. Vodnar ◽  
Laurian Vlase ◽  
...  
Keyword(s):  
In Silico ◽  
Docking Study ◽  
Biological Evaluation ◽  
Antifungal Drugs ◽  
Biologically Active ◽  
Molecular Docking Study ◽  
Candida Spp ◽  
In Silico Admet ◽  
In Silico Studies

In the context of an increased incidence of invasive fungal diseases, there is an imperative need of new antifungal drugs with improved activity and safety profiles. A novel series of acylhydrazones bearing a 1,4-phenylene-bisthiazole scaffold was designed based on an analysis of structures known to possess anti-Candida activity obtained from a literature review. Nine final compounds were synthesized and evaluated in vitro for their inhibitory activity against various strains of Candida spp. The anti-Candida activity assay revealed that some of the new compounds are as active as fluconazole against most of the tested strains. A molecular docking study was conducted in order to evaluate the binding poses towards lanosterol 14α-demethylase. An in silico ADMET analysis showed that the compounds possess drug-like properties and represent a biologically active framework that should be further optimized as potential hits.

Lepidine B & E as New Target Inhibitors from Lepidium Sativum Seeds Against Four Enzymes of the Pathogen Candida albicans: In Vitro and In Silico Studies

2020 ◽  
Vol 20 (1) ◽  
pp. 127-138
Author(s):  
Safia Gacemi ◽  
Khedidja Benarous ◽  
Santiago Imperial ◽  
Mohamed Yousfi
Keyword(s):  
Candida Albicans ◽  
Molecular Docking ◽  
Antifungal Activity ◽  
In Silico ◽  
Candida Rugosa ◽  
Antifungal Drugs ◽  
Yeast Cells ◽  
Lepidium Sativum ◽  
In Silico Studies

Background and Objective: The present paper aims to study the inhibition of Candida albicans growth as candidiasis treatment, using seeds of Lepidium sativum as source. Methods: In vitro assays were carried out on the antifungal activity of three kinds of extracts from L. sativum seeds against four strains of C. albicans, then testing the same phytochemicals on the inhibition of Lipase (LCR). A new in silico study was achieved using molecular docking, with Autodock vina program, to find binding affinity of two important and major lepidine alkaloids (lepidine E and B) towards the four enzymes secreted by C. albicans as target drugs, responsible of vitality and virulence of this yeast cells: Lipase, Serine/threonine phosphatase, Phosphomannose isomerase and Sterol 14-alpha demethylase (CYP51). Results: The results of the microdillution assay show that the hexanic and alkaloidal extracts have an antifungal activity with MICs: 2.25 mg/ml and 4.5mg/ml, respectively. However, Candida rugosa lipase assay gives a remarkable IC50 values for the hexanic extract (1.42± 0.04 mg/ml) followed by 1.7± 0.1 and 2.29 ± 0.09 mg/ml of ethyl acetate and alkaloidal extracts respectively. The molecular docking confirms a significant correlation between C. albicans growth and inhibition of crucial enzymes involved in the invasion mechanism and cellular metabolisms, for the first time there were an interesting and new positive results on binding modes of lepidine E and B on the four studied enzymes. Conclusion: Through this work, we propose Lepidine B & E as potent antifungal drugs.

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