1,2,4-triazole derivatives with morpholine; DFT study and antileishmanial activity

1,2,4-triazole derivatives with morpholine; 4-((3-methylthiophene–2-yl)methylenamino)-1-((4-(3-methylthiophene–2-yl)methylene amino)-1-(morpholinomethyl)-5-thioxo-4,5-dihydro-1H-1,2,4-triazole-3-yl)methyl)-3-(thiophene–2-ylmethyl)-1H-1,2,4-triazole-5(4H)-one (compound I) and 1-((1-(morpholinomethyl)–4-(5-nitrothiophene–2-yl)methyleneamino)-5-thioxo-4,5-dihydro-1H-1,2,4-triazole-3-yl)methyl)-4-((5-nitrothiophene–2-yl)methyleneamino)-3-(thiophene–2-ylmethyl)-1H-1,2,4-triazole-5(4H)-one (compound II), were optimized using a density functional theory (DFT) method with 6-311G(d,p) basis set and structural and spectral parameters were determined. In vitro antileishmanial activities of compounds were performed against Leishmania infantum promastigots by microdilution broth assay with Alamar Blue dye. Amphotericin B was used as standard drug. The results show that both compounds are antiparasitic and especially compound II has considerable antileishmanial activity due to the minimal inhibitory concentration value of 312 μg/mL.

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In-silico Molecular Docking and ADME/Pharmacokinetic Prediction Studies of Some Novel Carboxamide Derivatives as Anti-tubercular Agents

Chemistry Africa ◽

10.1007/s42250-020-00162-3 ◽

2020 ◽

Vol 3 (4) ◽

pp. 989-1000

Author(s):

Mustapha Abdullahi ◽

Shola Elijah Adeniji

Keyword(s):

Molecular Docking ◽

Binding Affinity ◽

In Silico ◽

Density Functional ◽

Docking Simulation ◽

Basis Set ◽

Hybrid Functional ◽

Standard Drug

AbstractMolecular docking simulation of thirty-five (35) molecules of N-(2-phenoxy)ethyl imidazo[1,2-a]pyridine-3-carboxamide (IPA) with Mycobacterium tuberculosis target (DNA gyrase) was carried out so as to evaluate their theoretical binding affinities. The chemical structure of the molecules was accurately drawn using ChemDraw Ultra software, then optimized at density functional theory (DFT) using Becke’s three-parameter Lee–Yang–Parr hybrid functional (B3LYP/6-311**) basis set in a vacuum of Spartan 14 software. Subsequently, the docking operation was carried out using PyRx virtual screening software. Molecule 35 (M35) with the highest binding affinity of − 7.2 kcal/mol was selected as the lead molecule for structural modification which led to the development of four (4) newly hypothetical molecules D1, D2, D3 and D4. In addition, the D4 molecule with the highest binding affinity value of − 9.4 kcal/mol formed more H-bond interactions signifying better orientation of the ligand in the binding site compared to M35 and isoniazid standard drug. In-silico ADME and drug-likeness prediction of the molecules showed good pharmacokinetic properties having high gastrointestinal absorption, orally bioavailable, and less toxic. The outcome of the present research strengthens the relevance of these compounds as promising lead candidates for the treatment of multidrug-resistant tuberculosis which could help the medicinal chemists and pharmaceutical professionals in further designing and synthesis of more potent drug candidates. Moreover, the research also encouraged the in vivo and in vitro evaluation study for the proposed designed compounds to validate the computational findings.

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Transformations of the Herbicide N-(1,1-dimethylpropynyl)-3,5-dichlorobenzamide in Soil

Weed Science ◽

10.1017/s0043174500034305 ◽

1970 ◽

Vol 18 (5) ◽

pp. 604-607 ◽

Cited By ~ 23

Author(s):

Roy Y. Yih ◽

Colin Swithenbank ◽

D. Harold McRae

Keyword(s):

Soil Moisture ◽

High Temperature ◽

Soil Moisture Content ◽

Chemical Change ◽

Herbicidal Activity ◽

Compound I ◽

Subsequent Hydrolysis ◽

Compound Ii ◽

Hydrolysis Of

Transformation of N-(1,1-dimethylpropynyl)-3,5-dichlorobenzamide (compound I) in soil occurs readily and two products are produced, initial cyclization giving 2-(3,5-dichlorophenyl)-4,4-dimethyl-5-methyleneoxazoline (compound II) followed by subsequent hydrolysis to N-(1,1-dimethylacetonyl)-3,5-dichlorobenzamide (compound III). These transformations can be brought aboutin vitro, the first step by means of acid or base, and the second by extended treatment with acid. The rate of cyclization and hydrolysis of compound I varies directly with soil temperature, being rapid at high temperature (37 C) and very slow at low temperature (5 C). The rate of chemical change of compound I in soil is influenced to a much greater degree by temperature than by soil moisture content. The effect of soil type on transformation of compound I was studied and compounds II and III were present in five of the six soils examined. The herbicidal activity of compounds II and III was negligible in comparison to compound I.

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A Theoretical Study of the Adsorption Process of B-aflatoxins Using Pyracantha koidzumii (Hayata) Rehder Biomasses

Toxins ◽

10.3390/toxins12050283 ◽

2020 ◽

Vol 12 (5) ◽

pp. 283

Author(s):

Abraham Méndez-Albores ◽

René Escobedo-González ◽

Juan Manuel Aceves-Hernández ◽

Perla García-Casillas ◽

María Inés Nicolás-Vázquez ◽

...

Keyword(s):

Functional Groups ◽

Electrostatic Interactions ◽

Density Functional ◽

Ph Value ◽

Theoretical Calculations ◽

Basis Set ◽

Hydroxyl Group ◽

Biosorption Process

Employing theoretical calculations with density functional theory (DFT) using the B3LYP/6-311++G(d,p) functional and basis set, the interaction of the aflatoxin B1 (AFB1) molecule and the functional groups present in the Pyracantha koidzumii biosorbent was investigated. Dissociation free energy and acidity equilibrium constant values were obtained theoretically both in solution (water) and gas phases. Additionally, the molecular electrostatic potential for the protonated molecules was calculated to verify the reactivity. Thus, methanol (hydroxyl group), methylammonium ion (amino group), acetate ion (carboxyl group), and acetone (carbonyl group), were used as representatives of the substrates present in the biomass; these references were considered using the corresponding protonated or unprotonated forms at a pH value of 5. The experimental infrared spectrophotometric data suggested the participation of these functional groups in the AFB1 biosorption process, indicating that the mechanism was dominated by electrostatic interactions between the charged functional groups and the positively charged AFB1 molecule. The theoretical determination indicated that the carboxylate ion provided the highest interaction energy with the AFB1 molecule. Consequently, an enriched biosorbent with compounds containing carboxyl groups could improve the yield of the AFB1 adsorption when using in vitro and in vivo trials.

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Identification of Suitable Agents against Adenine Phosphoribosyl Transferase for the Management of Leishmaniasis: Synthesis, Characterization and Computational Studies

Biointerface Research in Applied Chemistry ◽

10.33263/briac126.75037522 ◽

2021 ◽

Vol 12 (6) ◽

pp. 7503-7522

Keyword(s):

Leishmania Donovani ◽

Antileishmanial Activity ◽

Standard Drug ◽

Docking Analysis ◽

Equivalent Number ◽

In Silico Admet ◽

Drug Score ◽

Diphenyl Tetrazolium Bromide ◽

Genus Leishmania

A leishmaniasis is a group of diseases attributable to protozoan parasites of the genus Leishmania. It is a potential disease mostly occurring in developing nations. Various quinoline substituted derivatives (11a-f, 12a-f, and 13a-f) were synthesized by refluxing amino quinolines with an equivalent number of different alkylaminoethyl chlorides and evaluated for their in vitro antileishmanial activity against promastigotes forms of Leishmania donovani by using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] reduction assay. Compounds 11f (IC50 = 13.61μg/mL), 12f (IC50 = 11.92 μg/mL) and 13f (IC50 =10.41 μg/mL) have shown significant antileishmanial activity when compared with standard sitamaquine (IC50= 10.09 μg/mL). Furthermore, the molecular docking analysis targeting adenine phosphoribosyltransferase of Leishmania donovani exhibits significant binding interactions. In silico, ADMET predictions revealed that these compounds, i.e., 11f, 12f, and 13f, demonstrated good absorption as well as solubility characteristics with good drug-likeness and drug score values compared to the standard drug.

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Anti-Inflammatory, Anti-Diabetic, and Anti-Alzheimer’s Effects of Prenylated Flavonoids from Okinawa Propolis: An Investigation by Experimental and Computational Studies

Molecules ◽

10.3390/molecules23102479 ◽

2018 ◽

Vol 23 (10) ◽

pp. 2479 ◽

Cited By ~ 19

Author(s):

Md Shahinozzaman ◽

Nozomi Taira ◽

Takahiro Ishii ◽

Mohammad Halim ◽

Md Hossain ◽

...

Keyword(s):

Density Functional ◽

Nitrite Accumulation ◽

Standard Drug ◽

In Vitro Techniques ◽

Reactivity Descriptors ◽

Lipinski’S Rule ◽

Prenylated Flavonoids ◽

Ic50 Values ◽

Anti Inflammatory

Okinawa propolis (OP) and its major ingredients were reported to have anti-cancer effects and lifespan-extending effects on Caenorhabditis elegans through inactivation of the oncogenic kinase, p21-activated kinase 1 (PAK1). Herein, five prenylated flavonoids from OP, nymphaeol-A (NA), nymphaeol-B (NB), nymphaeol-C (NC), isonymphaeol-B (INB), and 3′-geranyl-naringenin (GN), were evaluated for their anti-inflammatory, anti-diabetic, and anti-Alzheimer’s effects using in vitro techniques. They showed significant anti-inflammatory effects through inhibition of albumin denaturation (half maximal inhibitory concentration (IC50) values of 0.26–1.02 µM), nitrite accumulation (IC50 values of 2.4–7.0 µM), and cyclooxygenase-2 (COX-2) activity (IC50 values of 11.74–24.03 µM). They also strongly suppressed in vitro α-glucosidase enzyme activity with IC50 values of 3.77–5.66 µM. However, only INB and NA inhibited acetylcholinesterase significantly compared to the standard drug donepezil, with IC50 values of 7.23 and 7.77 µM, respectively. Molecular docking results indicated that OP compounds have good binding affinity to the α-glucosidase and acetylcholinesterase proteins, making non-bonded interactions with their active residues and surrounding allosteric residues. In addition, none of the compounds violated Lipinski’s rule of five and showed notable toxicity parameters. Density functional theory (DFT)-based global reactivity descriptors demonstrated their high reactive nature along with the kinetic stability. In conclusion, this combined study suggests that OP components might be beneficial in the treatment of inflammation, type 2 diabetes mellitus, and Alzheimer’s disease.

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Synthesis, DFT Analysis, and Evaluation of Antibacterial and Antioxidant Activities of Sulfathiazole Derivatives Combined with In Silico Molecular Docking and ADMET Predictions

Biochemistry Research International ◽

10.1155/2021/7534561 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Yoseph Samuel ◽

Ankita Garg ◽

Endale Mulugeta

Keyword(s):

Molecular Docking ◽

In Silico ◽

Radical Scavenging ◽

Basis Set ◽

Diffusion Method ◽

Standard Drug ◽

Gram Negative ◽

E Coli ◽

In Silico Molecular Docking

Synthetic modifications of sulfathiazole derivatives become an interesting approach to enhance their biological properties in line with their applications. As a result, sulfathiazole derivatives become a good candidate and potential class of organic compounds to play an important role towards medicinal chemistry. In present study, one thiazole derivative and two new sulfathiazole derivatives are synthesized with 94% and 72–81% yields, respectively. Furthermore, the synthesized compounds were evaluated for their in vitro antibacterial activity against two Gram-negative (E. coli and P. aeruginosa) and two Gram-positive bacterial strains (S. pyogenes and S. aureus) by disk diffusion method. Among synthesized compounds, compound 11a showed potent inhibitory activity against Gram-negative, E. coli with 11.6 ± 0.283 mm zone of inhibition compared to standard drug sulfamethoxazole (15.7 ± 0.707 mm) at 50 mg/mL. The radical scavenging activities of these compounds were evaluated using DPPH radical assay, and compound 11a showed the strongest activity with IC50 values of 1.655 μg/mL. The synthesized compounds were evaluated for their in silico molecular docking analysis using S. aureus gyrase (PDB ID: 2XCT) and human myeloperoxidase (PDB ID: 1DNU) and were found to have minimum binding energy ranging from −7.8 to −10.0 kcal/mol with 2XCT and −7.5 to −9.7 with 1DNU. Compound 11a showed very good binding score −9.7 kcal/mol with both of the proteins and had promising alignment with in vitro results. Compound 11b also showed high binding scores with both proteins. Drug likeness and ADMET of synthesized compounds were predicted. The DFT analysis of synthesized compounds was performed using Gaussian 09 and visualized through Gauss view 6.0. The structural coordinates of the lead compounds were optimized using B3LYP/6–31 G (d,p) level basis set without any symmetrical constraints. Studies revealed that all the synthesized compounds might be candidates for further antibacterial and antioxidant studies.

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Folate-Targeted Polyacrylamide/Punicic Acid Nanomicelles for Flutamide Delivery in Prostate Cancer: Characterization, In Vitro Biological Evaluation, and its DFT Study

Recent Patents on Nanotechnology ◽

10.2174/1872210514666200513092614 ◽

2020 ◽

Vol 14 (4) ◽

pp. 360-374

Author(s):

Razieh Mirsafaei ◽

Jaleh Varshosaz ◽

Seyed N. Mirsattari

Keyword(s):

Prostate Cancer ◽

Density Functional ◽

Structural Parameters ◽

Density Functional Theory Method ◽

Biological Evaluation ◽

Chemotherapeutic Agents ◽

Vibrational Frequencies ◽

Basis Set ◽

Punicic Acid

Background: Targeted nanocarriers can be used for reducing the unwanted side effects of drugs in non-target organs. Punicic acid, the polyunsaturated fatty acid of pomegranate seed oil, has been shown to possess anti-cancer effects on prostate cancer and the study also covers recent patents related to prostate cancer. The objective of the current study was to synthesize a co-polymeric micelle for delivery of Flutamide (FL) in prostate cancer using Polyacrylamide (PAM) and Punicic Acid (PA). Methods: The co-polymer of PAM and PA was synthesized and conjugated to folic acid. The successful conjugation was studied computationally by the density functional theory method and was confirmed by the FT- IR and 1HNMR. The folate-PAMPA micelles produced by the film casting method were characterized physically. FL was loaded in the nanomicelles and its release test was done at different pH. The Critical Micelle Concentration (CMC) was measured by pyrene as a fluorescent probe. Their cellular uptake and cytotoxicity were evaluated on PC3 prostate cancer cells. The molecular geometry and vibrational frequencies of two different possibilities for conjugation were calculated using the B3LYP/6-31G basis set. Results: The CMC of the micelles and their particle size were 79.05 μg/ml and 88 nm, respectively. The resulting nanocarriers of FL showed significantly more cytotoxic effects than the free drug at a concentration of 25 μM. The calculated results showed that the optimized geometries could well reproduce the structural parameters, and the theoretical vibrational frequencies were in good agreement with the experimental values. Conclusion: Folate-PAMPA nanomicelles may be promising for the enhancement of FL cytotoxicity and seem to potentiate the effect of chemotherapeutic agents used in prostate cancer treatment.

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New Chalcone Derivative: Synthesis, Characterization, Computational Studies and Antioxidant Activity

Letters in Organic Chemistry ◽

10.2174/1570178616666181130163115 ◽

2019 ◽

Vol 17 (1) ◽

pp. 46-53

Author(s):

Reşat Ustabaş ◽

Nevin Süleymanoğlu ◽

Namık Özdemir ◽

Nuran Kahriman ◽

Ersan Bektaş ◽

...

Keyword(s):

Antioxidant Activity ◽

Density Functional ◽

Computational Study ◽

Dft Method ◽

Basis Set ◽

Basis Sets ◽

Isomeric Form ◽

Compound I ◽

Chalcone Derivative ◽

Reducing Ability

A new chalcone derivative, called as 1-(4-(benzylideneamino)phenyl)-3-(furan-2-yl)prop-2- en-1-one (I), was synthezised and characterized by spectral methods (infrared (IR) and proton and carbon- 13 nuclear magnetic resonance (1H- and 13C-NMR) spectroscopy). A computational study was performed by the density functional theory (DFT) method. Spectral data of compound I optimized by using 6-311G(d,p) and 6-311++G(d,p) basis sets were obtained by 6-311++G(d,p) basis set. The E-Z isomerism for newly synthesized chalcone derivative was investigated by considering four isomeric form, E/E, E/Z, Z/E and Z/Z. The results show that, as assumed and thus named, the chalcone derivative is in the E/E form. In addition, quantum chemical parameters were calculated by using DFT method with 6-311++G(d,p) basis set. Antioxidant activity of compound I was determined by the ferric reducing ability of plasma (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay methods. Compound I has low antioxidant activity.

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In Vitro and In Silico Antioxidant Activity of Novel Peptides Prepared from Paeonia Ostii ‘Feng Dan’ Hydrolysate

Antioxidants ◽

10.3390/antiox8100433 ◽

2019 ◽

Vol 8 (10) ◽

pp. 433 ◽

Cited By ~ 1

Author(s):

Min Wang ◽

Cong Li ◽

Haoyu Li ◽

Zibo Wu ◽

Bang Chen ◽

...

Keyword(s):

Antioxidant Activity ◽

Free Radical ◽

In Silico ◽

Density Functional ◽

Radical Scavenging ◽

Free Radical Scavenging ◽

Basis Set ◽

Superior Performance ◽

Antioxidant Peptides

Antioxidant peptides derived from natural products have superior performance and broader application prospects. In this study, five novel antioxidant peptides were prepared from Paeonia ostii (P. ostii) seed meal, moreover the bioactive and the relationship between structure and properties of antioxidant peptides were elucidated by quantum chemical calculations. The free radical-scavenging activities were used as indexes to purify and concentrate the antioxidant peptides through five proteases and separation techniques. FSAP (Phe-Ser-Ala-Pro), PVETVR (Pro-Val-Glu-Thr-Val-Arg), QEPLLR (Gln-Glu-Pro-Leu-Leu-Arg), EAAY (Glu-Ala-Ala-Tyr) and VLRPPLS (Val-Leu-Arg-Pro-Pro-Leu-Ser) were identified by nano liquid chromatography–tandem mass spectrometry (LC-MS/MS). In vitro antioxidant activity test, EAAY exhibited the highest 2, 2’-azino-bis (ABTS) and hydroxyl radical-scavenging activity of 98.5% ± 1.1% and 61.9% ± 1.3%, respectively (p < 0.01), at 0.5 mg/mL. In silico calculations were carried out using the density functional theory (DFT) with the B3LYP/6-31G* basis set. According to natural bond orbital (NBO) analysis, the bioactivity of free-radical scavenging of the peptides was presumed. Moreover, the antioxidant peptides demonstrated no obvious cytotoxicity to L929 fibroblast cells. Therefore, the peptides from P. ostii seed by-products might potentially have excellent uses in functional foods, nutraceuticals and pharmacological products.

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(E)-2-{[(2-Aminophenyl)imino]methyl}-5-(benzyloxy)phenol and (Z)-3-benzyloxy-6-{[(5-chloro-2-hydroxyphenyl)amino]methylidene}cyclohexa-2,4-dien-1-one

Acta Crystallographica Section E Crystallographic Communications ◽

10.1107/s2056989018005662 ◽

2018 ◽

Vol 74 (5) ◽

pp. 737-742

Author(s):

Nadir Ghichi ◽

Ali Benboudiaf ◽

Chawki Bensouici ◽

Yacine DJebli ◽

Hocine Merazig

Keyword(s):

Hydrogen Bond ◽

Schiff Base ◽

Density Functional ◽

Tautomeric Form ◽

Three Dimensional ◽

Molecular Structures ◽

Compound I ◽

Phenyl Rings ◽

Imine Bond ◽

Compound Ii

The title Schiff base compounds, C20H18N2O2(I) and C20H16ClNO3(II), were synthesized from 4-benzyloxy-2-hydroxybenzaldehyde by reaction with 1,2-diaminobenzene for (I), and condensation with 2-amino-4-chlorophenol for (II). Compound (I) adopts the enol–imine tautomeric form with anEconfiguration about the C=N imine bond. In contrast, theo-hydroxy Schiff base (II), is in the keto–imine tautomeric form with aZconfiguration about the CH—NH bond. Neither molecule is planar. In (I), the central benzene ring makes dihedral angles of 46.80 (10) and 78.19 (10)° with the outer phenylamine and phenyl rings, respectively, while for (II), the corresponding angles are 5.11 (9) and 58.42 (11)°, respectively. The molecular structures of both compounds are affected by the formation of intramolecular contacts, an O—H...N hydrogen bond for (I) and an N—H...O hydrogen bond for (II); each contact generates anS(6) ring motif. In the crystal of (I), strong N—H...O hydrogen bonds form zigzag chains of molecules along theb-axis direction. Molecules are further linked by C—H...π interactions and offset π–π contacts and these combine to form a three-dimensional network. The density functional theory (DFT) optimized structure of compound (II), at the B3LYP/6–311+G(d) level, confirmed that the keto tautomeric form of the compound, as found in the structure determination, is the lowest energy form. The antioxidant capacities of both compounds were determined by the cupric reducing antioxidant capacity (CUPRAC) process.

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