scholarly journals Novel Pyrimidinone Linked 1,2,3-Triazole Scaffolds as Anti-Microbial and Antioxidant Agents: Synthesis, In-vitro and In-silico Studies

2021 ◽  
pp. 477-491
Author(s):  
Narendra Kumar Maddali ◽  
I. V. Kasi Viswanath ◽  
Y. L. N. Murthy ◽  
Vasavi Malkhed ◽  
Vani Kondaparthi ◽  
...  
Keyword(s):  
Computational Study ◽  
Binding Energies ◽  
Assay Method ◽  
Dpph Assay ◽  
Antimicrobial Studies ◽  
Antioxidant Agents ◽  
In Silico Studies ◽  
Almost All ◽  
Dehydrosqualene Synthase

The present study states the synthesis of a novel series of pyrimidinone linked 1,2,3-triazole scaffolds by click chemistry method. Further, the synthesized compounds were evaluated for their antimicrobial studies against S. aureus and S. pneumoniae. Among the synthesized compounds, almost all compounds demonstrated significant antimicrobial activity against S. aureus, S. pneumoniae, E.coli and P. aeruginosa, as evident from the zone of inhibition resulted. In addition, synthesised compounds were screened for their antioxidant activity by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay method. Furthermore, computational study was performed to understand the interactions between synthesised compounds with dehydrosqualene synthase of Staphylococcus aureus (PDB ID: 2ZCS) and few Compound revealed the highest binding energies ΔG = -9.5, -9.8, and -10.1 Kcal/mol.

scholarly journals Design, Synthesis, Characterization, Computational Study and In-vitro Antioxidant and Anti-inflammatory Activities of Few Novel Pyrazol-3-one Derivatives

2021 ◽  
pp. 220-231
Author(s):  
Aziz Unnisa ◽  
B. Anupama ◽  
Humera Banu ◽  
Syeda B. Fatima ◽  
K. N. V. Chenchu Lakshmi ◽  
...  
Keyword(s):  
Computational Study ◽  
Efficacy And Safety ◽  
Dpph Assay ◽  
Design Synthesis ◽  
Synthetic Compounds ◽  
Highly Active ◽  
Anti Inflammatory ◽  
Further Development ◽  
Mutagenic Compound

Aim: To design, synthesize and perform computational study on a few Novel pyrazol-3-one derivatives. Study design:  Experimental study. Methodology: A series of 6-aryl substituted pyrimidine azodyes were synthesized by coupling phenyl pyrimidine 2-amine with different aromatic amines. The synthetic compounds were screened for their in-vitro antioxidant and anti-inflammatory activities. The Computational study of designed compounds was done by OCHEM, Molinspiration cheminformatics, Datawarrior, and Swiss ADME. DPPH assay was used to determine the antioxidant activity and heat hemolysis method for anti-inflammatory activity. Results: Molinspiration, Data Warrior, Ochem which are helpful to predict molecule general properties, bioactive scores, toxicity, and drug-likeness. Data Warrior results inferred that the compounds possess moderately active towards mutagenic (compound 2, 11), reproductive (compound 6, 7, 8), and highly active towards Tumorogenic (compound 2) toxicities. OCHEM results showed that most of the synthesized compounds were found to be non-inhibitors of all the subtypes of cytochrome P450 except compound 8. All compounds under this study were effective scavengers of free radicals except the compounds 1, 2, 6, 10. Invitro Anti-inflammatory studies have shown that the compounds (6, 7, 8, 9, 13) active toward heat hemolysis. Conclusion: The synthesized compounds were comprehensively studied and targets were identified rendering them as lead molecules for further development of newer agents with greater efficacy and safety.

Non-Phenolic Antioxidant Compounds from Buddleja asiatica

2008 ◽  
Vol 63 (7-8) ◽  
pp. 483-491 ◽  
Author(s):  
Mortada M. El-Sayed ◽  
El-Sayed S. Abdel-Hameed ◽  
Wafaa S. Ahmed ◽  
Eman A. El-Wakil
Keyword(s):  
Methanol Extract ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Antioxidant Compounds ◽  
Scavenging Activity ◽  
Chemical Analyses ◽  
Dpph Assay ◽  
Antioxidant Agents ◽  
Total Antioxidant

The methanol extract of the leaves of Buddleja asiatica Lour. (Loganiaceae) showed antioxidant activity toward the well known in vitro antioxidant tests such as total antioxidant capacity by the phosphomolybdenum method, free radical scavenging activity by the 1,1- diphenyl-2-picrylhydrazyl scavenging assay (DPPH assay) and hydrogen peroxide scavenging methods. Due to the high scavenging activity of the n-butanol successive fraction toward DPPH and H2O2 (SC50 = 11.99 and 18.54 μg/ml, respectively), this extract was subjected to chromatographic separation and isolation. Four non-phenolic compounds were isolated and identified on the basis of spectroscopic and chemical analyses: 1-O-ß-D-glucopyranosyl- 2-methoxy-3-(2-hydroxy-triaconta-3,12-dienoate)-glycerol (1), 3-O-[α-l-rhamnopyranosyl- (1→4)-ß-d-glucopyranosyl-(1→3)]-[ß-d-glucopyranosyl-(1→2)]-ß-d-fucopyranosyl-olean- 11,13(18)-diene-3ß,23,28-triol (2), 3-O-[α-l-rhamnopyranosyl-(1→4)-ß-d-glucopyranosyl- (1→4)-ß-d-glucopyranosyl-(1→3)]-ß-d-fucopyranosyl-olean-11,13(18)-diene-3ß,23,28-triol (3), and 3-O-[α-l-rhamnopyranosyl-(1→4)-ß-d-glucopyranosyl-(1→3)]-[ß-d-xylopyranosyl- (1→2)]-ß-d-glucuronopyranosyl-acid-olean-11,13(18)-diene-3ß,23,28-triol (4). The four compounds were evaluated as antioxidant agents using the three antioxidant bioassay tests.

Pyrazole Schiff Base Hybrids as Anti-Malarial Agents: Synthesis, In Vitro Screening and Computational Study

2018 ◽  
Vol 21 (3) ◽  
pp. 194-203 ◽  
Author(s):  
Shilpy Aggarwal ◽  
Deepika Paliwal ◽  
Dhirender Kaushik ◽  
Girish Kumar Gupta ◽  
Ajay Kumar
Keyword(s):  
Schiff Base ◽  
Antimalarial Activity ◽  
Computational Study ◽  
Docking Study ◽  
Docking Studies ◽  
Binding Energies ◽  
Study Results ◽  
Wide Range ◽  
Parasite Plasmodium Falciparum

Background: Malaria is one of the most vital infectious diseases caused by protozoan parasites of the Plasmodium genus. As P. falciparum, the cause of most of the severe cases of malaria, is increasingly resistant to available drugs such as amodioquine, chloroquine, artemisinin, and antifolates, there is an urgent need to identify new targets for chemotherapy. Objective: This study screened novel pyrazole derivatives carrying iminium & benzothiazole group for antimalarial potential against P. falciparum chloroquine sensitive (3D7) strain. Materials & Methods: Several pyrazole schiff base hybrids with a wide range of substitution have been synthesized via condensation of substituted aniline with substituted 4-formylpyrazole and evaluated for their in vitro antimalarial activity against asexual blood stages of human malaria parasite, Plasmodium falciparum. The interaction of these conjugate hybrids was also investigated by molecular docking studies in the binding site of P. falciparum cystein protease falcipain-2. The pharmacokinetic properties were also studied using ADME prediction. Results: Among all compounds, 6bf and 6bd were found to be potential molecules with EC50 1.95µg/ml and 1.98µg/ml respectively. Docking study results reveal that the pyrazole schiff base derivatives occupy the PfFP binding sites and they show good interactions with significant values of binding energies. Conclusion: We provide evidence which implicates pyrazole Schiff base hybrids as potential prototypes for the development of antimalarial agents.

scholarly journals In Silico Drug Discovery of 4-Hyroxypanduratin A, 6-Gingerol and Luteolin Targeting Nipah Virus

2021 ◽  
pp. 477-484
Author(s):  
Anurag Verma ◽  
Piyush Mittal ◽  
Milind S. Pande ◽  
Neelanchal Trivedi
Keyword(s):  
Fusion Protein ◽  
In Silico ◽  
Virus Entry ◽  
Nipah Virus ◽  
Binding Energies ◽  
Viral Agent ◽  
In Silico Studies ◽  
Viral Target ◽  
Dietary Food

Nipah Virus is a zoo tonic virus and has re-emerged again with more deadliness. NiV has infected many animals and humans worldwide and a huge loss to life has been faced. NiV contains a Fusion protein on its outer membrane which helps in the virus entry into the host cell. This fusion protein is a virulent factor and is a major anti-viral target. Many medicinal plants have been used against viral diseases, current research aims towards the potential of three daily dietary food elements that can be used as an anti-viral agent. In-silico studies are performed with 4-hyroxypanduratin A, 6-gingerol and Luteolin against the NiV-F and binding energies were calculated. It was reported that these phyto-compounds have good negative binding energies and they have the promising potential against Nipah Virus. Further in-vitro research can be performed with these phyto-compounds to design a specific drug against Nipah Virus.

New Benzodioxole-based Pyrazoline Derivatives: Synthesis and Anticandidal, In silico ADME, Molecular Docking Studies

2018 ◽  
Vol 16 (1) ◽  
pp. 82-92 ◽  
Author(s):  
Ahmet Özdemir ◽  
Belgin Sever ◽  
Mehlika Dilek Altıntop
Keyword(s):  
In Silico ◽  
Fungal Infections ◽  
Computational Study ◽  
Docking Studies ◽  
In Vivo Studies ◽  
Heme Group ◽  
In Silico Studies ◽  
Nih 3T3

Background: Azoles are commonly used in the treatment and prevention of fungal infections. They suppress fungal growth by acting on the heme group of lanosterol 14α-demethylase enzyme (CYP51), thus blocking the biosynthesis of ergosterol. </P><P> Objectives: Due to the importance of pyrazolines in the field of antifungal drug design, we aimed to design and synthesize new pyrazoline-based anticandidal agents. Methods: New pyrazoline derivatives were synthesized via the reaction of 1-(chloroacetyl)-3-(2- thienyl)-5-(1,3-benzodioxol-5-yl)-2-pyrazoline with aryl thiols. These compounds were evaluated for their in vitro antifungal effects on Candida species. Docking studies were performed to predict the affinity of the most effective anticandidal agents to substrate binding site of CYP51. Furthermore, MTT assay was performed to determine the cytotoxic effects of the compounds on NIH/3T3 mouse embryonic fibroblast cell line. A computational study for the prediction of ADME properties of all compounds was also carried out. Results: Compounds 5, 8, 10 and 12 were found as the most potent anticandidal agents against Candida albicans and Candida glabrata in this series with the same MIC values of ketoconazole and they also exhibited low toxicity against NIH/3T3 cells. Docking results indicated that all these compounds showed good binding affinity into the active site of CYP51. In particular, chloro substituted compounds 8 and 12 bind to CYP51 through direct coordination with the heme group. According to in silico studies, compound 8 only violated one parameter of Lipinski’s rule of five, making it a potential orally bioavailable agent. Conclusion: Compound 8 was defined as a promising candidate for further in vitro and in vivo studies.

scholarly journals Chemical Profiles and Pharmacological Properties with in Silico Studies on Elatostema papillosum Wedd

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 809 ◽  
Author(s):  
Md. Zia Uddin ◽  
Arkajyoti Paul ◽  
Ahmed Rakib ◽  
Saad Ahmed Sami ◽  
Shafi Mahmud ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Serotonin Receptor ◽  
Computational Study ◽  
Biological Activities ◽  
Binding Affinities ◽  
In Silico Studies ◽  
Cox 2 ◽  
Cox 1

The current study attempted, for the first time, to qualitatively and quantitatively determine the phytochemical components of Elatostema papillosum methanol extract and their biological activities. The present study represents an effort to correlate our previously reported biological activities with a computational study, including molecular docking, and ADME/T (absorption, distribution, metabolism, and excretion/toxicity) analyses, to identify the phytochemicals that are potentially responsible for the antioxidant, antidepressant, anxiolytic, analgesic, and anti-inflammatory activities of this plant. In the gas chromatography-mass spectroscopy analysis, a total of 24 compounds were identified, seven of which were documented as being bioactive based on their binding affinities. These seven were subjected to molecular docking studies that were correlated with the pharmacological outcomes. Additionally, the ADME/T properties of these compounds were evaluated to determine their drug-like properties and toxicity levels. The seven selected, isolated compounds displayed favorable binding affinities to potassium channels, human serotonin receptor, cyclooxygenase-1 (COX-1), COX-2, nuclear factor (NF)-κB, and human peroxiredoxin 5 receptor proteins. Phytol acetate, and terpene compounds identified in E. papillosum displayed strong predictive binding affinities towards the human serotonin receptor. Furthermore, 3-trifluoroacetoxypentadecane showed a significant binding affinity for the KcsA potassium channel. Eicosanal showed the highest predicted binding affinity towards the human peroxiredoxin 5 receptor. All of these findings support the observed in vivo antidepressant and anxiolytic effects and the in vitro antioxidant effects observed for this extract. The identified compounds from E. papillosum showed the lowest binding affinities towards COX-1, COX-2, and NF-κB receptors, which indicated the inconsequential impacts of this extract against the activities of these three proteins. Overall, E. papillosum appears to be bioactive and could represent a potential source for the development of alternative medicines; however, further analytical experiments remain necessary.

scholarly journals Phytochemical Analysis and Antioxidant Potential of Rhizome Extracts of Curcuma amada Roxb and Curcuma caesia Roxb

2019 ◽  
Vol 9 (5) ◽  
pp. 123-126
Author(s):  
Mamta Yadav ◽  
K. Kalyan Saravanan
Keyword(s):  
Manufacturing Industry ◽  
Antioxidant Activities ◽  
Perennial Herb ◽  
Assay Method ◽  
Phytochemical Analysis ◽  
Human Beings ◽  
Dpph Assay ◽  
Test Protocol ◽  
Curcuma Amada

Plants have served human beings as a natural source for treatments and therapies from ancient times, amongst them medicinal herbs have gain attention because of its wide use and less side effects. In the recent years plant research has increased throughout the world and a huge amount of evidences have been collected to show immense potential of medicinal plants used in various traditional systems. Curcuma amada Roxb (C. amada, Zingiberaceae) is a perennial, rhizomatous, aromatic herb commonly known as Amada or Amahaldi or mango ginger due to the raw mango-like aroma of the rhizome. It is used medicinally as a coolant, astringent and to promote digestion. Curcuma caesia Roxb (C. caesia, Zingiberacea) is a perennial herb with bluish black rhizomes commonly known as black turmeric and are traditionally used in treatment of various ailments and metabolic disorders like leukoderma, asthma, tumours, piles, bronchitis, etc. in Indian system of medicine. The aim of the present study was to evaluate in vitro antioxidant activities and qualitative and quantitative phytochemical analysis of rhizome of C. amada and C. caesia collected from Bhopal region of Madhya Pradesh. Qualitative analysis of various phytochemical constituents and quantitative analysis of total phenolics and flavonoids were determined by the well-known test protocol available in the literature. The in vitro antioxidant activity of methanolic extract of the rhizome was assessed against DPPH assay method using standard protocols. Phytochemical analysis revealed the presence of phenols, flavonoids, tannins, saponins, alkaloids. The total flavonoids content of methanolic rhizomes extract of C. caesia and C. amada was found to be 2.752 and 2.920 mg/100mg respectively. The activities of methanolic rhizomes extract against DPPH assay method were concentration dependent with IC 50 values of ascorbic acid and extracts 14.11 and 170.81, 63.69μg/ml respectively. The diverse array of phytochemicals present in the plant thus suggests its therapeutic potentials which may be explored in drug manufacturing industry as well as in traditional medicine. Keywords: Curcuma amada, Curcuma caesia, Zingiberacea, Phytochemical analysis, Antioxidant

scholarly journals In-vitro anti-diabetic activity and in-silico studies of binding energies of palmatine with alpha-amylase, alpha-glucosidase and DPP-IV enzymes

Pharmacia ◽  
2020 ◽  
Vol 67 (4) ◽  
pp. 363-371
Author(s):  
Patrick Okechukwu ◽  
Mridula Sharma ◽  
Wen Hui Tan ◽  
Hor Kuan Chan ◽  
Kavita Chirara ◽  
...  
Keyword(s):  
In Silico ◽  
Binding Energies ◽  
Alpha Amylase ◽  
Binding Interactions ◽  
Inhibiting Effect ◽  
Dpp Iv ◽  
In Silico Studies ◽  
Significant Difference ◽  
Alpha Glucosidase

Palmatine a protoberberine alkaloid has been previously reported to possess in vivo antidiabetic and antioxidant property. The aim of the experiment is to evaluate the in vitro antidiabetic activity and in-silico studies of the binding energies of Palmatine, acarbose, and Sitagliptin with the three enzymes of alpha-amylase, alpha-glucosidase, and dipeptidyl peptidase-IV (DPP-IV). The in vitro antidiabetic study was done by evaluating the inhibitory effect of palmatine on the activities of alpha-amylase, alpha-glucosidase, and DPP-IV. Acarbose, and sitagliptin was used as standard drug. The molecular docking study was performed to study the binding interactions of palmatine with alpha-glucosidase, a-amylase, and DPP-IV. The binding interactions were compared with the standard compounds Sitagliptin and acarbose. Palmatine with IC50 (1.31 ± 0.27 µM) showed significant difference of (&lt; 0.0001) higher inhibiting effect on alpha-amylase and weak inhibiting effect on alpha-glucosidase enzyme with IC50 (9.39 ± 0.27 µM) and DPP-IV with IC50 (8.7 ± 1.82 µM). Palmatine possess inhibition effect on the three enzymes.

scholarly journals Selection the Drug Efficacy of Oroidin Derivatives as Hsp90 Inhibitors by Computer Aided Drug Design Method

2020 ◽  
pp. 630-651
Author(s):  
Subhajit Sarkar ◽  
Rajesh Kumar Das
Keyword(s):  
Chemical Potential ◽  
Design Method ◽  
Molecular Descriptor ◽  
Dipole Moments ◽  
Binding Energies ◽  
Basis Set ◽  
Toxicity Tests ◽  
In Vitro Test ◽  
In Silico Studies

Heat shock protein 90 (Hsp90) is a conserved molecular chaperone associated with regulation of hundreds of client proteins that are key drivers, regulators and promoters of numerous refractory diseases including cancer. Consequently, Hsp90 is a significant target for the development of harmless anticancer therapies. Marine organisms are the rich source of pharmacological important compounds, especially oroidin. Oroidin, a pyrrole-2-aminoimidazole alkaloid, isolated from the marine sponge Agelas oroides, binds ATP pocket of Hsp90 and suppresses the ATPase activity of the protein. Natural product oroidin was selected as potent inhibitor of Hsp90 and its drug candidature was accordingly improved by substituting various functional groups. Virtual screenings were done through in silico studies, carried out on thirty nine derivatives of oroidin. DFT study was performed with Gaussian16, UB3LYP/6-311G++ (d, p) basis set to investigate the quantum mechanical parameters such as HOMO-LUMO energies, dipole moments. Derived parameters like ionization potential, electron affinity, softness-hardness, chemical potential and electrophilicity index were also calculated. Using AutoDock 4.0 programme, we studied docking of the thirty-nine designed derivatives with macromolecule Hsp90 and recorded the binding energy values of the best conformation out of nine in each docked compound. ADME predictions, molecular descriptor properties, and theoretical toxicity tests were evaluated using preADMET, molinspiration, and OSIRIS property explorer web tools respectively. We found twenty eight derived compounds, each docked at the same region of Hsp90, possessing higher binding energies compare to the precursor oroidin. Seven of them qualified all the rules of drug candidature and could be safe in using as effective drugs for cancer treatment. This study suggests that these compounds could be synthesized for in vitro test and may leads to a novel anticancer therapeutics.

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