Novel coumarin-6-sulfonamides as apoptotic anti-proliferative agents: synthesis, in vitro biological evaluation, and QSAR studies

Objective: The aim of this study was to evaluate 2,4-dichlorobenzoic acid derivatives as antimicrobial agents through in vitro, QSAR and molecular docking studies. Methods: The compounds were subjected to in vitro antimicrobial screening by test tube dilution method and the structural characteristics governing the antimicrobial potential were studied using QSAR methodology. These compounds were also screened for docking simulation to find out binding confirmation of reported compounds with PDB 1aj0 and 5fsa using AutoDock tools and discovery studio. Results: The antimicrobial evaluation data indicated that compounds 13 and 18 were found to be the most effective against all the bacterial strains and Aspergillus niger while compounds 1 and 14 exhibited more antifungal potential against Candida albicans. QSAR studies confirmed the role of molar refractivity and Balaban index (J) as controlling parameters for antimicrobial potential. Molecular modeling study revealed that compounds interact with the active site of PDB by hydrophobic, hydrogen bonding, and Van der Wall interactions. Conclusion: These test compounds were identified as potent candidates for the control of microbial strains tested, and structural relationship with activity may provide valuable information for further design and synthesis of compounds with antimicrobial potential.

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2-Amino-4-arylthiazole Derivatives as Anti-giardial Agents: Synthesis, Biological Evaluation and QSAR Studies

Open Chemistry ◽

10.1515/chem-2015-0127 ◽

2015 ◽

Vol 13 (1) ◽

Cited By ~ 6

Author(s):

Raul Mocelo-Castell ◽

Carlos Villanueva-Novelo ◽

David Cáceres-Castillo ◽

Ruben M. Carballo ◽

Ramiro F. Quijano-Quiñones ◽

...

Keyword(s):

Positive Control ◽

Biological Evaluation ◽

Toxicity Tests ◽

Data Set ◽

Qsar Analysis ◽

Qsar Studies ◽

Modified Method ◽

Acute Toxicity Tests ◽

Low Toxicity

AbstractA series of seven 2-amino-4-arylthiazoles were prepared following Hantzsch’s modified method under microwave irradiation. A set of 50 derivatives was obtained and the in vitro activity against Giardia intestinalis was evaluated. The results on the biological activity revealed that, in general, the N-(5-bromo-4-aryl-thiazol-2-yl)-acetamide scaffold showed high bioactivity. In particular, compounds 6e (IC50 = 0.39 μM) and 6b (IC50 = 0.87 μM) were found to be more potent than the positive control metronidazole. Citoxicity and acute toxicity tests performed showed low toxicity and high selectivity of the most active compounds (6e SI = 139, 6b SI = 52.3). A QSAR analysis was applied to a data set of 37 obtained 2-amino-4-arylthiazoles derivatives and the best model described a strongly correlation between the anti-giardiasic activity and molecular descriptors as E2M, RDF115m, F10, MATS6v, and Hypnotic-80, with high statistical quality. This finding indicates that N-substituted aminothiazole scaffold should be investigated for the development of highly selective anti-giardial agent.

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Synthesis, 2D-QSAR Studies and Biological Evaluation of Quinazoline Derivatives as Potent Anti-Trypanosoma cruzi Agents

Medicinal Chemistry ◽

10.2174/1573406414666181005145042 ◽

2019 ◽

Vol 15 (3) ◽

pp. 265-276 ◽

Cited By ~ 3

Author(s):

Mariela Bollini ◽

Ana M. Bruno ◽

María E. Niño ◽

Juan J. Casal ◽

Leandro D. Sasiambarrena ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Chronic Phase ◽

Biological Evaluation ◽

Significant Activity ◽

Qsar Studies ◽

2D Qsar ◽

Starting Point ◽

Quinazoline Derivatives

Background: Chagas disease affects about 7 million people worldwide. Only two drugs are currently available for the treatment for this parasite disease, namely, benznidazol (Bzn) and nifurtimox (Nfx). Both drugs have limited curative power in the chronic phase of the disease. Therefore, continuous research is an urgent need so as to discover novel therapeutic alternatives. Objective: The development of safer and more efficient therapeutic anti-T. cruzi drugs continues to be a major goal in trypanocidal chemotherapy. Method: Synthesis, 2D-QSAR and drug-like physicochemical properties of a set of quinazolinone and quinazoline derivatives were studied as trypanocidal agents. All compounds were screened in vitro against Trypanosoma cruzi (Tulahuen strain, Tul 2 stock) epimastigotes and bloodstream trypomastigotes. Results: Out of 34 compounds synthesized and tested, six compounds (5a, 5b, 9b, 9h, 13f and 13p) displayed significant activity against both epimastigotes and tripomastigotes, without exerting toxicity on Vero cells. Conclusion: The antiprotozoal activity of these quinazolinone and quinazoline derivatives represents an interesting starting point for a medicinal chemistry program aiming at the development of novel chemotherapies for Chagas disease.

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Synthesis, Biological Evaluation and 2D-QSAR Studies of Novel 6-Oxo-Pyridine-3-Carboxamide Derivatives as Antimicrobial and Antifungal Agents

International Journal of Chemistry ◽

10.5539/ijc.v8n1p49 ◽

2015 ◽

Vol 8 (1) ◽

pp. 49 ◽

Cited By ~ 1

Author(s):

Hend M. El-Sehrawi ◽

Dalia H. Soliman ◽

Maha M. Khalifa ◽

Omneya M. El-Bakry

Keyword(s):

Antifungal Agents ◽

Binding Mode ◽

Biological Evaluation ◽

Reference Drug ◽

Qsar Studies ◽

2D Qsar ◽

Antimicrobial Evaluation ◽

Antibacterial And Antifungal ◽

Derivatives Of

In this study twenty six novel derivatives of 6-oxo-pyridine-3-carboxamide were synthesized and evaluated as antibacterial and antifungal agents. Synthesis of the 2-amino-4-methyl-6-oxo-N,1-diphenyl-1,6-dihydropyridine-3-carboxamide 1 was carried out by reacting equimolar quantities of acetoacetanilide and cyanoacetanilide in ethanol using triethylamine as a catalyst. The results of the in vitro antimicrobial evaluation showed that, the 6-oxo-N,1-diphenyl-5-(p-tolyldiazenyl)-1,6-dihydropyridine-3-carboxamide, 5c displayed broad-spectrum antibacterial activity which was equipotent to both Ampicillin and Gentamicin against the tested bacteria. Moreover, compounds 3a, 5c and 9b were equipotent to the reference drug, Amphotericin B, against Aspergillus fumigatus (MIC = 1.95µg/ml). 2D QSAR studies were carried out in order to correlate the observed activity to the binding mode of these compounds, in addition to their molecular properties that might be controlling their activities.

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Potential antitumoral 3,4-dihydropyrimidin-2-(1H)-ones: synthesis, in vitro biological evaluation and QSAR studies

RSC Advances ◽

10.1039/c6ra14596e ◽

2016 ◽

Vol 6 (88) ◽

pp. 84943-84958 ◽

Cited By ~ 10

Author(s):

Mariana Matias ◽

Gonçalo Campos ◽

Adriana O. Santos ◽

Amílcar Falcão ◽

Samuel Silvestre ◽

...

Keyword(s):

Anticancer Agents ◽

Biological Evaluation ◽

Lower Toxicity ◽

Qsar Studies ◽

Medical Need

The search for novel anticancer agents with higher selectivity and lower toxicity remains a medical need.

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Synthesis, Characterization and in vitro Biological Evaluation of a New Schiff Base Derived from Drug and its Complexes with Transition Metal Ions

Revista de Chimie ◽

10.37358/rc.18.7.6393 ◽

2018 ◽

Vol 69 (7) ◽

pp. 1678-1681

Author(s):

Amina Mumtaz ◽

Tariq Mahmud ◽

M. R. J. Elsegood ◽

G. W. Weaver

Keyword(s):

Schiff Base ◽

Transition Metal ◽

Metal Ions ◽

Metal Complexes ◽

Transition Metal Complexes ◽

Free Ligand ◽

Transition Metal Ions ◽

Biological Evaluation ◽

Pyridoxal Hydrochloride

New series of copper (II), cobalt (II), zinc (II), nickel (II), manganese (II), iron (II) complexes of a novel Schiff base were prepared by the condensation of sulphadizine and pyridoxal hydrochloride. The ligand and metal complexes were characterized by utilizing different instrumental procedures like microanalysis, thermogravimetric examination and spectroscopy. The integrated ligand and transition metal complexes were screened against various bacteria and fungus. The studies demonstrated the enhanced activity of metal complexes against reported microbes when compared with free ligand.

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Synthesis and Biological Evaluation of Amoxicillin Loaded Hybrid Material Composite Spheres Against Methicillin-Resistant Staphylococcus aureus

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666201221143537 ◽

2020 ◽

Vol 21 ◽

Author(s):

Muhammad Arfat Yameen ◽

Amir Zeb ◽

Raza E Mustafa ◽

Sana Mushtaq ◽

Nargis Aman ◽

...

Keyword(s):

Mtt Assay ◽

Hybrid Material ◽

Ag Nanoparticles ◽

Hybrid Composite ◽

Synthesis Method ◽

Biological Evaluation ◽

Vitro Assay ◽

Cytotoxicity Studies ◽

Material Composite

Background: Incoherent use of antibiotics has led toward resistance in MRSA, which is becoming multidrugresistant with high rate of virulence in the community and hospital settings. Objective: Synergistic anti-MRSA activity was investigated in this study for hybrid material composite spheres of amoxicillin, Ag nanoparticles and chitosan which were prepared by one-step synthesis method and various characterizations were performed. Methods: Antimicrobial-susceptibility assay on MRSA was achieved by disc diffusion and agar dilution techniques while agar well diffusion was used for hybrid composite spheres. The in vitro and cytotoxicity studies was done by skin abrasion mouse model and MTT assay on RD cell respectively. Results: All isolates were resistant with the tested antibiotics except vancomycin. MIC against MRSA showed high resistance with amoxicillin from 4 to 128 mg L-1. The mean diameter of chitosan spheres and Ag nanoparticles was 02 mm and 277 nm respectively. Morphology of spheres was uneven, varied, porous and irregular in SEM and Ag nanoparticles presence and formation was also seen in micrograph. No substantial interface among drug, nanoparticles and polymer was found in XRD and IR showed characteristic peaks of all compound in the formulation. The in vitro assay showed augmented anti-MRSA activity with amoxicillin loaded hybrid composite spheres (22-29 mm). A significant reduction in microbial burden (~6.5 log10 CFU ml-1) was seen in vivo with loaded hybrid composite spheres formulation. The MTT assay indicated no potential cytotoxicity with hybrid composite spheres. Conclusion: Synergistic effect, amoxicillin, new hybrid formulation, anti-MRSA activity, composite spheres. nanoparticles.

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Hybrid Design of Isonicotinic Acid Hydrazide Derivatives: Machine Learning Studies, Synthesis and Biological Evaluation of their Antituberculosis Activity

Current Drug Discovery Technologies ◽

10.2174/1570163816666190411110331 ◽

2020 ◽

Vol 17 (3) ◽

pp. 365-375

Author(s):

Vasyl Kovalishyn ◽

Diana Hodyna ◽

Vitaliy O. Sinenko ◽

Volodymyr Blagodatny ◽

Ivan Semenyuta ◽

...

Keyword(s):

Machine Learning ◽

Isonicotinic Acid ◽

Acid Hydrazide ◽

Predictive Ability ◽

Antitubercular Activity ◽

Biological Evaluation ◽

Starting Point ◽

Binary Classifiers ◽

Synthesis And Biological Evaluation

Background: Tuberculosis (TB) is an infection disease caused by Mycobacterium tuberculosis (Mtb) bacteria. One of the main causes of mortality from TB is the problem of Mtb resistance to known drugs. Objective: The goal of this work is to identify potent small molecule anti-TB agents by machine learning, synthesis and biological evaluation. Methods: The On-line Chemical Database and Modeling Environment (OCHEM) was used to build predictive machine learning models. Seven compounds were synthesized and tested in vitro for their antitubercular activity against H37Rv and resistant Mtb strains. Results: A set of predictive models was built with OCHEM based on a set of previously synthesized isoniazid (INH) derivatives containing a thiazole core and tested against Mtb. The predictive ability of the models was tested by a 5-fold cross-validation, and resulted in balanced accuracies (BA) of 61–78% for the binary classifiers. Test set validation showed that the models could be instrumental in predicting anti- TB activity with a reasonable accuracy (with BA = 67–79 %) within the applicability domain. Seven designed compounds were synthesized and demonstrated activity against both the H37Rv and multidrugresistant (MDR) Mtb strains resistant to rifampicin and isoniazid. According to the acute toxicity evaluation in Daphnia magna neonates, six compounds were classified as moderately toxic (LD50 in the range of 10−100 mg/L) and one as practically harmless (LD50 in the range of 100−1000 mg/L). Conclusion: The newly identified compounds may represent a starting point for further development of therapies against Mtb. The developed models are available online at OCHEM http://ochem.eu/article/11 1066 and can be used to virtually screen for potential compounds with anti-TB activity.

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Design, Synthesis, Molecular Docking and Biological Evaluation of 1-(benzo[d]thiazol-2-ylamino)(phenyl)methyl)naphthalen-2-ol Derivatives as Antiproliferative Agents

Letters in Organic Chemistry ◽

10.2174/1570178616666190408101233 ◽

2019 ◽

Vol 16 (10) ◽

pp. 837-845

Author(s):

Sandhya Jonnala ◽

Bhaskar Nameta ◽

Murthy Chavali ◽

Rajashaker Bantu ◽

Pallavi Choudante ◽

...

Keyword(s):

Molecular Docking ◽

Inhibitory Activity ◽

Chinese Hamster Ovary Cells ◽

Chinese Hamster ◽

Mouse Skin ◽

Coupling Reaction ◽

Binding Mode ◽

Biological Evaluation ◽

Design Synthesis

A class of 1-((benzo[d]thiazol-2-ylamino)(phenyl)methyl)naphthalen-2-ol derivatives (4a-t) has been synthesized in good yields through a three component coupling reaction. The newly synthesized compounds were evaluated for their in vitro antiproliferative activity against five cell lines such as DU145 (human prostate cancer), MDA-MB-B231 (human breast cancer), SKOV3 (human ovarian cancer), B16-F10 (mouse skin melanoma) and CHO-K1 (Chinese hamster ovary cells), a noncancerous cell line. In vitro inhibitory activity indicates that compounds 4a, 4b, 4c, 4d, 4g, 4j, and 4o exhibited potent anti-proliferative behavior. Among them, compounds 4g, 4j and 4o found to be the most active members exhibiting remarkable growth inhibitory activity. Molecular docking facilitates to investigate the probable binding mode and key active site interactions in tubulins α and β proteins. The docking results are complementary to experimental results.

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Structure-Based Design, Synthesis, Biological Evaluation and Molecular Docking Study of 4-Hydroxy-N'-methylenebenzohydrazide Derivatives Acting as Tyrosinase Inhibitors with Potentiate Anti-Melanogenesis Activities

Medicinal Chemistry ◽

10.2174/1573406415666190724142951 ◽

2020 ◽

Vol 16 (7) ◽

pp. 892-902 ◽

Cited By ~ 3

Author(s):

Aida Iraji ◽

Mahsima Khoshneviszadeh ◽

Pegah Bakhshizadeh ◽

Najmeh Edraki ◽

Mehdi Khoshneviszadeh

Keyword(s):

Molecular Docking ◽

Active Site ◽

Competitive Inhibition ◽

Docking Study ◽

Biological Evaluation ◽

Primary Response ◽

Ratio Method ◽

Molecular Docking Study ◽

Metal Chelating

Background: Melanogenesis is a process of melanin synthesis, which is a primary response for the pigmentation of human skin. Tyrosinase is a key enzyme, which catalyzes a ratelimiting step of the melanin formation. Natural products have shown potent inhibitors, but some of these possess toxicity. Numerous synthetic inhibitors have been developed in recent years may lead to the potent anti– tyrosinase agents. Objective: A number of 4-hydroxy-N'-methylenebenzohydrazide analogues with related structure to chalcone and tyrosine were constructed with various substituents at the benzyl ring of the molecule and evaluate as a tyrosinase inhibitor. In addition, computational analysis and metal chelating potential have been evaluated. Methods: Design and synthesized compounds were evaluated for activity against mushroom tyrosinase. The metal chelating capacity of the potent compound was examined using the mole ratio method. Molecular docking of the synthesized compounds was carried out into the tyrosine active site. Results: Novel 4-hydroxy-N'-methylenebenzohydrazide derivatives were synthesized. The two compounds 4c and 4g showed an IC50 near the positive control, led to a drastic inhibition of tyrosinase. Confirming in vitro results were performed via the molecular docking analysis demonstrating hydrogen bound interactions of potent compounds with histatidine-Cu+2 residues with in the active site. Kinetic study of compound 4g showed competitive inhibition towards tyrosinase. Metal chelating assay indicates the mole fraction of 1:2 stoichiometry of the 4g-Cu2+ complex. Conclusion: The findings in the present study demonstrate that 4-Hydroxy-N'- methylenebenzohydrazide scaffold could be regarded as a bioactive core inhibitor of tyrosinase and can be used as an inspiration for further studies in this area.

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