SINTESIS, UJI AKTIVITAS SITOTOKSIK IN VITRO DAN MOLECULAR DOCKING SENYAWA 1-(4-KLOROBENZOIL)-1,3-DIMETILUREA

Senyawa 1-(4-klorobenzoil)-1,3-dimetilurea telah dirancang, disintesis, diidentifikasi struktur, dan diuji aktivitas sitotoksik secara in vitro. Simulasi docking dilakukan dengan memposisikan senyawa ke dalam sisi aktif reseptor Checkpoint kinase 1 (Chk1) untuk menentukan model pengikatan ligan reseptor. Sintesis 1-(4-klorobenzoil)-1,3-dimetilurea dilakukan lewat reaksi asilasi antara 1,3-dimetilurea dan 4-klorobenzoil klorida. Kemurnian produk hasil sintesis ditentukan dengan metode Kromatografi Lapis Tipis (KLT).Identifikasi struktur dilakukan dengan spektrofotometer UV, FT-IR dan spektrometer NMR. Hasil uji antiproliferatif menunjukkan bahwa senyawa 1-(4-klorobenzoil)-1,3-dimetilurea memiliki aktivitas sitotoksik terhadap sel HeLa yang lebih baik dibandingkan dengan kontrol positif yaitu hidroksiurea. Senyawa 1-(4-klorobenzoil)-1,3-dimetilurea dengan potensi aktivitas sitotoksik ini dapat menjadi agen antikanker yang potensial. Kata kunci: 1-(4-klorobenzoil)-1,3-dimetilurea, molecular docking, sintesis, aktivitas sitotoksik, hidroksiurea A novel 1-(4-chlorobenzoyl)-1,3-dimethylurea has been designed, synthesized, structurally determined, and the in vitro cytotoxic activity was evaluated. Docking simulation was performed to position this compound into the Checkpoint kinase 1 (Chk1) active site to determine the probable binding model. Synthesis of 1-(4-chlorobenzoyl)-1,3-dimethylurea was completed by acylation reaction between 1,3-dimethylurea and 4-chlorobenzoyl chloride. The purity of synthesized product was determined by Thin Layer Chromatography. Structure identification was performed by UV spectrophotometer, FT-IR and NMR spectrometer. Antiproliferative assay result demonstrated that this compound possessed good cytotoxic activity against HeLa cells, which is comparable to the positive control, hydroxyurea. This compound with potent cytotoxic activity might be a potential anticancer agent. Keywords: 1-(4-chlorobenzoyl)-1,3-dimethylurea, molecular docking, synthesis, cytotoxic activity

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POCl3 Mediated Syntheses, Pharmacological Evaluation and Molecular Docking Studies of Some Novel Benzofused Thiazole Derivatives as a Potential Antioxidant and Anti-inflammatory Agents

Current Chemical Biology ◽

10.2174/2212796813666191118100520 ◽

2020 ◽

Vol 14 (1) ◽

pp. 58-68

Author(s):

Dattatraya G. Raut ◽

Sandeep B. Patil ◽

Prafulla B. Choudhari ◽

Vikas D. Kadu ◽

Anjana S. Lawand ◽

...

Keyword(s):

Molecular Docking ◽

Antioxidant Activities ◽

Research Work ◽

Radical Scavenging ◽

Docking Simulation ◽

Thiazole Derivatives ◽

Binding Model ◽

Antioxidant Agents ◽

Anti Inflammatory

Background: The present research work is focused on the development of alternative antioxidant and anti-inflammatory agents. The review of the literature reveals that many benzofused thiazole analogues have been used as lead molecules for the design and development of therapeutic agent, including anticancer, anti-inflammatory, antioxidant and antiviral. The synthesized benzofused thiazole derivatives are evaluated for in vitro antioxidant, anti-inflammatory activities and molecular docking study. Thus, the present research work aims to synthesize benzofused thiazole derivatives and to test their antioxidant and antiinflammatory activities. Objective: To design and synthesize an alternative antioxidant and anti-inflammatory agents. Methods: The substituted benzofused thiazoles 3a-g were prepared by cyclocondensation reaction of appropriate carboxylic acid with 2-aminothiophenol in POCl3 and heated for about 2-3 h to offer benzofused thiazole derivatives 3a-g. All the newly synthesized compounds were in vitro screened for their anti-inflammatory and antioxidant activities by using a known literature method. Results: At the outset, the study of in vitro indicated that the compounds code 3c, 3d and 3e possessed distinct anti-inflammatory activity as compared to a standard reference. All the tested compounds show potential antioxidant activity against one or more reactive (H2O2, DPPH, SO and NO) radical scavenging species. Additionally, docking simulation is further performed to the position of compounds 3d & 3e into the anti-inflammatory active site to determine the probable binding model. Conclusion: New anti-inflammatory and antioxidant agents were needed; it has been proved that benzofused thiazole derivatives were 3c, 3d and 3e constituted as an interesting template for the evaluation of new anti-inflammatory agents and an antioxidant’s work also may provide an interesting template for further development.

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In-vitro bactericidal activity of a novel plant source Plumeria pudica against some human and fish pathogenic bacteria

Current Drug Discovery Technologies ◽

10.2174/1570163817666200727101300 ◽

2020 ◽

Vol 17 ◽

Author(s):

Shubhaisi Das ◽

Sunanda Burman ◽

Goutam Chandra

Keyword(s):

Ethyl Acetate ◽

Bioactive Compounds ◽

Pathogenic Bacteria ◽

Ethyl Acetate Extract ◽

Positive Control ◽

Leaf Extracts ◽

Ms Analysis ◽

Ft Ir ◽

Aldehyde Groups

Background: The only remedy for up surging problem of antibiotic resistance is the discovery of antibacterial agents of natural origin. Objective: The present study was aimed at finding antibacterial potential of crude and solvent extracts of mature leaves of Plumeria pudica. Methods: Antibacterial activity of three different solvent extracts were evaluated in four human and four fish pathogenic bacteria by measuring the zone of inhibition and determining Minimum Inhibitory Concentration and Minimum Bactericidal Concentration values. Standard antibiotics were used as positive control. Preliminary phytochemical screening of most effective extract i.e., ethyl acetate extract, Fourier Transform Infra Red analysis and GC-MS analysis of the Thin Layer Chromatographic (TLC) fraction of ethyl acetate extract were done meticulously. All experiments were done thrice and analyzed statistically. Results: Crude leaf extracts and solvent extracts caused good inhibition of bacterial growth in all selected bacteria. Ethyl acetate extract showed highest inhibition zones in all tested strains with maximum inhibition (19.50±0.29 mm) in Escherichia coli (MTCC 739). MBC/MIC of the extracts indicated that all three solvent extracts were bactericidal. Preliminary phytochemical tests revealed the presence of tannins, steroids and alkaloids and FT-IR analysis revealed presence of many functional groups namely alcoholic, amide, amine salt and aldehyde groups. From the GC-MS analysis of TLC fraction of ethyl acetate extract five different bioactive compounds e.g., 2,4-ditert –butylphenyl 5-hydroxypentanoate, Oxalic acid; allyl nonyl ester, 7,9-Ditert-butyl-1-oxaspiro(4,5)deca-6,9-diene-2,8-dione, Dibutyl phthalate and 2,3,5,8-tetramethyl-decane were identified. Conclusion: Leaf extracts of P. pudica contain bioactive compounds that can be used as broad spectrum bactericidal agent.

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Ingol and Ingenol-Type Diterpenes from Euphorbia trigona Miller with Keratinocyte Inhibitory Activity

Plants ◽

10.3390/plants10061206 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1206

Author(s):

Reham Hammadi ◽

Norbert Kúsz ◽

Csilla Zsuzsanna Dávid ◽

Zoltán Behány ◽

László Papp ◽

...

Keyword(s):

Liquid Chromatography ◽

Cytotoxic Activity ◽

Inhibitory Activity ◽

High Performance ◽

Skin Condition ◽

Positive Control ◽

Active Species ◽

The European Union ◽

Ingenol Mebutate

Ingenol mebutate, isolated from Euphorbia peplus, is an ingenane-type diterpenoid, primarily used for the topical treatment of actinic keratosis, a premalignant skin condition. The aim of our work was to investigate other Euphorbia species to find structurally similar diterpenes that can be used as alternatives to ingenol mebutate. Pharmacological investigation of Euphorbia candelabrum, Euphorbia cotinifolia, Euphorbia ramipressa, and Euphorbia trigona revealed the potent keratinocyte (HPV-Ker cell line) inhibitory activity of these spurge species. From the methanolic extract of the aerial parts of Euphorbia trigona Miller, the most active species, five ingol (1–5) and four ingenane-type diterpenoids (6–9) were isolated by various chromatographic separation techniques, including open column chromatography, vacuum liquid chromatography, thin-layer chromatography, and high-performance liquid chromatography. The structures of the compounds were determined by NMR spectroscopic analysis and by comparison of the assignations with the literature data. The cytotoxic activity of the compounds against keratinocytes was tested in vitro by using ingenol mebutate as a positive control. Among the isolated compounds, two ingenane derivatives (6 and 7) exhibited remarkably stronger cytotoxic activity (IC50 values 0.39 μM and 0.32 μM, respectively) on keratinocytes than ingenol mebutate (IC50 value 0.84 μM). These compounds could serve as starting materials for further investigations to find alternatives to Picato® (with active substance ingenol mebutate), which was withdrawn from marketing authorization in the European Union.

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Structural Basis of Binding and Rationale for the Potent Urease Inhibitory Activity of Biscoumarins

BioMed Research International ◽

10.1155/2014/935039 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 6

Author(s):

Muhammad Arif Lodhi ◽

Sulaiman Shams ◽

Muhammad Iqbal Choudhary ◽

Atif Lodhi ◽

Zaheer Ul-Haq ◽

...

Keyword(s):

Molecular Docking ◽

Active Sites ◽

Docking Simulation ◽

Cysteine Residue ◽

Structural Basis ◽

Bacillus Pasteurii ◽

Nickel Ions ◽

Jack Bean ◽

Uv Visible

Urease belongs to a family of highly conserved urea-hydrolyzing enzymes. A common feature of these enzymes is the presence of two Lewis acid nickel ions and reactive cysteine residue in the active sites. In the current study we examined a series of biscoumarins1–10for their mechanisms of inhibition with the nickel containing active sites of Jack bean andBacillus pasteuriiureases. All these compounds competitively inhibited Jack bean urease through interaction with the nickel metallocentre, as deduced from Michaelis-Menten kinetics, UV-visible absorbance spectroscopic, and molecular docking simulation studies. Some of the compounds behaved differently in case ofBacillus pasteuriiurease. We conducted the enzyme kinetics, UV-visible spectroscopy, and molecular docking results in terms of the known protein structure of the enzyme. We also evaluated possible molecular interpretations for the site of biscoumarins binding and found that phenyl ring is the major active pharmacophore. The excellent in vitro potency and selectivity profile of the several compounds described combined with their nontoxicity against the human cells and plants suggest that these compounds may represent a viable lead series for the treatment of urease associated problems.

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Design, Synthesis, Anticancer Evaluation, and Molecular Docking Studies of Novel Benzoxazole Linked 1,3,4-Oxadiazoles

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666210706120203 ◽

2021 ◽

Vol 21 ◽

Author(s):

Sushmitha Bujji ◽

Praveen Kumar E ◽

Sree Kanth Sivan ◽

Manjunatha DH ◽

Subhashini N.J.P.

Keyword(s):

Molecular Docking ◽

Anticancer Activity ◽

Cell Lines ◽

Research Work ◽

Docking Simulation ◽

Research Field ◽

Spectroscopic Techniques ◽

Cancer Disease ◽

Amide Derivatives

Background: Cancer disease is making a serious concern globally. Global cancer occurrence is steadily increasing every year. There is always a persistent need to develop new anticancer drugs with reduced side effects or act synergistically with the existing chemotherapeutics. Objective: Benzoxazoles are fused bicyclic nitrogen and oxygen-containing heterocyclic compounds and are considered biologically privileged scaffolds. We designed a synthetic route to link the benzoxazoles with oxadiazoles resulting in a better pharmacophore for anticancer activity. Methods: A series of novel amide derivatives of benzoxazole linked 1,3,4-oxadiazoles (10a-j) were synthesized and characterized by 1H NMR, 13C NMR, and mass spectroscopic techniques. The biological properties of the compounds were screened in vitro against four different tumor cell lines. Results: The results suggest that the compound 10b having 3,4,5-trimethoxy substitution on the phenyl ring exhibited potent anticancer activity in three cell lines (A549 = 0.13 ± 0.014 µM, MCF-7 = 0.10 ± 0.013 µM and HT-29 = 0.22 ± 0.017 µM). Notably, among the synthesized derivatives, compounds 10b, 10c, 10f, 10g, and 10i exhibited potent anticancer activity than the control IC50 in the range of 0.11 ± 0.02 to 0.93 ± 0.034 µM. Molecular docking simulation results showed compounds were stabilized by hydrogen bond and π-π interactions with the protein. Conclusion: The molecules showed comparable binding affinities with standard Combretastatin-A4. The present research work is preliminary and needs further studies to take the synthesized compounds to the next level in the cancer research field.

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Synthesis, characterization, in vitro cytotoxic activity and molecular docking of dinuclear gold(I) complexes with terephthalaldehyde bis(thiosemicarbazones)

Polyhedron ◽

10.1016/j.poly.2021.115498 ◽

2021 ◽

Vol 210 ◽

pp. 115498

Author(s):

Ignacio del Águila ◽

M. Antonia Mendiola ◽

Sayantan Pradhan ◽

Chittaranjan Sinha ◽

Elena López-Torres

Keyword(s):

Molecular Docking ◽

Cytotoxic Activity

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Molecular docking simulation and in vitro studies on estrogenic activities of flavonoids from leaves of Carya cathayensis Sarg

Steroids ◽

10.1016/j.steroids.2020.108726 ◽

2020 ◽

Vol 163 ◽

pp. 108726

Author(s):

Jing-Jing Lu ◽

Fang-Mei Zhou ◽

Xu-Jiao Hu ◽

Jing-Jing Fang ◽

Cai-Xia Liu ◽

...

Keyword(s):

Molecular Docking ◽

Docking Simulation ◽

In Vitro Studies ◽

Molecular Docking Simulation ◽

Carya Cathayensis ◽

Carya Cathayensis Sarg

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A Tiered Female Ovarian Toxicity Screening Identifies Toxic Effects of Checkpoint Kinase 1 Inhibitors on Murine Growing Follicles

Toxicological Sciences ◽

10.1093/toxsci/kfaa118 ◽

2020 ◽

Vol 177 (2) ◽

pp. 405-419

Author(s):

Jingshan Xu ◽

Yingzheng Wang ◽

Alexandra E Kauffman ◽

Yaqi Zhang ◽

Yang Li ◽

...

Keyword(s):

Pharmaceutical Compounds ◽

Reproductive Age ◽

Toxicity Screening ◽

In Vivo Models ◽

Checkpoint Kinase ◽

Ovarian Toxicity ◽

Checkpoint Kinase 1 ◽

Screening Approach

Abstract Ovarian toxicity (ovotoxicity) is one of the major side effects of pharmaceutical compounds for women at or before reproductive age. The current gold standard for screening of compounds’ ovotoxicity largely relies on preclinical investigations using whole animals. However, in vivo models are time-consuming, costly, and harmful to animals. Here, we developed a 3-tiered ovotoxicity screening approach starting from encapsulated in vitro follicle growth (eIVFG) and screened for the potential ovotoxicity of 8 preclinical compounds from AstraZeneca (AZ). Results from Tiers 1 to 2 screenings using eIVFG showed that the first 7 tested AZ compounds, AZ-A, -B, -C, -D, -E, -F, and -G, had no effect on examined mouse follicle and oocyte reproductive outcomes, including follicle survival and development, 17β-estradiol secretion, ovulation, and oocyte meiotic maturation. However, AZ-H, a preclinical compound targeting the checkpoint kinase 1 inhibitor to potentiate the anticancer effects of DNA-damaging agents, significantly promoted granulosa cell apoptosis and the entire growing follicle atresia at clinically relevant concentrations of 1 and 10 μM. The more targeted explorations in Tier 2 revealed that the ovotoxic effect of AZ-H primarily resulted from checkpoint kinase 1 inhibition in granulosa cells. Using in vivo mouse model, the Tier 3 screening confirmed the in vitro ovotoxicities of AZ-H discovered in Tiers 1 and 2. Also, although AZ-H at 0.1 μM alone was not ovotoxic, it significantly exacerbated gemcitabine-induced ovotoxicities on growing follicles. Taken together, our study demonstrates that the tiered ovotoxicity screening approach starting from eIVFG identifies and prioritizes pharmaceutical compounds of high ovotoxicity concern.

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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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Actinidia macrospermaC. F. Liang (a Wild Kiwi): Preliminary Study of Its Antioxidant and Cytotoxic Activities

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/180262 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7

Author(s):

Yin Lu ◽

Xiangtao Du ◽

Lidan Lai ◽

Hao Jin

Keyword(s):

Antioxidant Activity ◽

Cytotoxic Activity ◽

Biological Activities ◽

Positive Control ◽

Total Phenolic ◽

Cytotoxic Activities ◽

Dependent Manner ◽

Etoac Extract ◽

Total Antioxidant

The antioxidant potential ofActinidia macrospermaC. F. Liang (Actinidiaceae) was investigated in vitro for total phenolic content, along with total antioxidant activity (TAA), 1,1-diphenyl 2-picryl hydrazyl (DPPH), and lipid peroxidation (LP). The results indicated that different polarity extracts ofA. macrospermaexhibit different biological activities, which depends mainly on the presence of phenolic compounds. The antioxidant activity was in the following decreasing order: MeOH extract > EtOAc extract > aqueous extract > CHCl3extract > Hexane extract. Moreover, the cytotoxic activity of this plant by MTT dye assay using SMMC-7721 has been determined also. The hexane, EtOAc, and CHCl3extracts showed cytotoxicity in a dose-dependent manner. Methanol and aqueous extracts, however, showed weak activities in this test. And a very significant cytotoxic activity, not significantly different from the positive control of quercetin, was observed in CHCl3extract.

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