Syntheses, in vitro urease inhibitory activities of urea and thiourea derivatives of tryptamine, their molecular docking and cytotoxic studies

Background: Designing drug candidates against the urease enzyme, which has been found responsible for many pathological disorders in human beings as well as in animals, was done by insilico means. Methods: Studies were carried out on a designed library of diosmin derivatives with the help of Schrodinger’s maestro package of molecular docking software against a crystallographic complex of plant enzyme Jack bean urease (PDB ID: 3LA4). Best twelve derivatives of diosmin were selected for synthesis by considering their interaction energy along with docking score and were further investigated for antioxidant, urease inhibitory and Anti-H. pylori activity by in- vitro method along with ADMET analysis. Results: In-vitro results of series concluded compounds D2a, D2d and D7 (IC50 12.6 ± 0.002, 14.14 ± 0.001 and 15.64 ± 0.012 µM respectively in urease inhibition and 5.195 ± 0.036, 5.39 ± 0.020 and 5.64± 0.005 µM in antioxidant behavior against DPPH) were found to be significantly potent with excellent docking score -11.721, -10.795, -10.188 and binding energy -62.674, -63.352, -56.267 kJ/ mol as compared to standard drugs thiourea and acetohydroxamic acid (-3.459, -3.049 and -21.156 kJ/mol and - 17.454 kJ/mol) whereas compounds D2b, D5b, D5d and D6 were found moderate in urease inhibitory activity. Conclusions: Selected candidates from the outcome of in-vitro urease inhibitory were further examined for anti- H. pylori activity by a well diffusion method against H. pylori bacterium (DSM 4867). Compound D2a showed good anti-H. Pylori activity with a zone of inhibition 10.00 ± 0.00 mm and MIC value 500µg/mL as compared to standard drug acetohydroxamic acid having a zone of inhibition 9.00 ± 0.50mm and MIC 1000µg/mL. In- silico studies played an important role in designing the potent ligands against urease protein as well as in explaining the binding pattern of designed and synthesized ligand within the active pocket of jack bean urease protein. ADMET studies were also carried out to check the drug similarity of designed compounds by the means of quikprop module of molecular docking software. Hence, the present investigation studies will provide a new vision for the discovery of potent agents against H. pylori and urease associated diseases.

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Synthesis, Molecular Docking, and In Vitro Investigation of 1,1'-Diaryl- 3,3'-(p-phenylenedicarbonyl) dithioureas as Urease Inhibitors

Letters in Organic Chemistry ◽

10.2174/1570178616666191004111058 ◽

2020 ◽

Vol 17 (4) ◽

pp. 254-259

Author(s):

Hummera Rafique ◽

Fizza Tahira ◽

Syeda Zar Afshan ◽

Muhammad Naseem ◽

Naghmana Kausar ◽

...

Keyword(s):

Molecular Docking ◽

Binding Mode ◽

Docking Studies ◽

Inhibitor Binding ◽

In Vitro Investigation ◽

Urease Enzyme ◽

Inhibitory Activities ◽

Urease Inhibitory ◽

High Yields

Synthesis of some 1,1'-diaryl-3,3'-(p-phenylenedicarbonyl)dithioureas was accomplished in two steps. Dithioureas were prepared under inert conditions with significantly high yields. Inhibitory activity of dithiourea compounds was investigated against urease enzyme. All the synthesized compounds were evaluated for their urease inhibitory activities, and molecular docking studies were carried out to ascertain the inhibitor binding mode with the enzyme. All the compounds displayed moderate to significant urease inhibitory activities.

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Synthetic nicotinic/isonicotinic thiosemicarbazides: In vitro urease inhibitory activities and molecular docking studies

Bioorganic Chemistry ◽

10.1016/j.bioorg.2018.04.004 ◽

2018 ◽

Vol 79 ◽

pp. 34-45 ◽

Cited By ~ 12

Author(s):

Basharat Ali ◽

Khalid Mohammed Khan ◽

Arshia ◽

Kanwal ◽

Shafqat Hussain ◽

...

Keyword(s):

Molecular Docking ◽

Docking Studies ◽

Molecular Docking Studies ◽

Inhibitory Activities ◽

Urease Inhibitory

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Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase

Scientific Reports ◽

10.1038/s41598-021-91473-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Fariba Peytam ◽

Ghazaleh Takalloobanafshi ◽

Toktam Saadattalab ◽

Maryam Norouzbahari ◽

Zahra Emamgholipour ◽

...

Keyword(s):

Molecular Docking ◽

Docking Study ◽

Rat Small Intestine ◽

Molecular Docking Study ◽

Design Synthesis ◽

Mild Conditions ◽

Glucosidase Inhibitors ◽

Inhibitory Activities

AbstractIn an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their inhibitory activities against yeast α-glucosidase enzyme were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which encouraged us to perform further studies on α-glucosidase enzymes obtained from rat as a mammal source. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against both Saccharomyces cerevisiae α-glucosidase (IC50 = 16.4 ± 0.36 μM) and rat small intestine α-glucosidase (IC50 = 45.0 ± 8.2 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.

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Phosphate Derivatives of 3-Carboxyacylbetulin: SynThesis, In Vitro Anti-HIV and Molecular Docking Study

Biomolecules ◽

10.3390/biom10081148 ◽

2020 ◽

Vol 10 (8) ◽

pp. 1148

Author(s):

Krzysztof Marciniec ◽

Elwira Chrobak ◽

Aleksandra Dąbrowska ◽

Ewa Bębenek ◽

Monika Kadela-Tomanek ◽

...

Keyword(s):

Molecular Docking ◽

Betulinic Acid ◽

Strong Interactions ◽

Molecular Docking Study ◽

Gag Protein ◽

Terminal Domain ◽

Derivatives Of ◽

Anti Hiv ◽

Hiv 1

Lupane-type pentacyclic triterpenes such as betulin and betulinic acid play an important role in the search for new therapies that would be effective in controlling viral infections. The aim of this study was the synthesis and evaluation of in vitro anti-HIV-1 activity for phosphate derivatives of 3-carboxyacylbetulin 3–5 as well as an in silico study of new compounds as potential ligands of the C-terminal domain of the HIV-1 capsid–spacer peptide 1 (CA-CTD-SP1) as a molecular target of HIV-1 maturation inhibitors. In vitro studies showed that 28-diethoxyphosphoryl-3-O-(3′,3′-dimethylsuccinyl)betulin (compound 3), the phosphate analog of bevirimat (betulinic acid derivative, HIV-1 maturation inhibitor), has IC50 (half maximal inhibitory concentration) equal to 0.02 μM. Compound 3 inhibits viral replication at a level comparable to bevirimat and is also more selective (selectivity indices = 1250 and 967, respectively). Molecular docking was used to examine the probable interaction between the phosphate derivatives of 3-carboxyacylbetulin and C-terminal domain (CTD) of the HIV-1 capsid (CA)–spacer peptide 1 (SP1) fragment of Gag protein, designated as CTD-SP1. Compared with interactions between bevirimat (BVM) and the protein, an increased number of strong interactions between ligand 3 and the protein, generated by the phosphate group, were observed. These compounds might have the potential to also inhibit SARS-CoV2 proteins, in as far as the intrinsically imprecise docking scores suggest.

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Synthesis, Antimicrobial Activity and Molecular Docking of Novel Thiourea Derivatives Tagged with Thiadiazole, Imidazole and Triazine Moieties as Potential DNA Gyrase and Topoisomerase IV Inhibitors

Molecules ◽

10.3390/molecules25122766 ◽

2020 ◽

Vol 25 (12) ◽

pp. 2766 ◽

Cited By ~ 1

Author(s):

Heba E. Hashem ◽

Abd El-Galil E. Amr ◽

Eman S. Nossier ◽

Elsayed A. Elsayed ◽

Eman M. Azmy

Keyword(s):

Antimicrobial Activity ◽

Molecular Docking ◽

Antimicrobial Agents ◽

Biological Activities ◽

Topoisomerase Iv ◽

Thiourea Derivatives ◽

E Coli ◽

Cytotoxicity Studies ◽

Ic50 Values

To develop new antimicrobial agents, a series of novel thiourea derivatives incorporated with different moieties 2–13 was designed and synthesized and their biological activities were evaluated. Compounds 7a, 7b and 8 exhibited excellent antimicrobial activity against all Gram-positive and Gram-negative bacteria, and the fungal Aspergillus flavus with minimum inhibitory concentration (MIC) values ranged from 0.95 ± 0.22 to 3.25 ± 1.00 μg/mL. Furthermore, cytotoxicity studies against MCF-7 cells revealed that compounds 7a and 7b were the most potent with IC50 values of 10.17 ± 0.65 and 11.59 ± 0.59 μM, respectively. On the other hand, the tested compounds were less toxic against normal kidney epithelial cell lines (Vero cells). The in vitro enzyme inhibition assay of 8 displayed excellent inhibitory activity against Escherichia coli DNA B gyrase and moderate one against E. coli Topoisomerase IV (IC50 = 0.33 ± 1.25 and 19.72 ± 1.00 µM, respectively) in comparison with novobiocin (IC50 values 0.28 ± 1.45 and 10.65 ± 1.02 µM, respectively). Finally, the molecular docking was done to position compound 8 into the E. coli DNA B and Topoisomerase IV active pockets to explore the probable binding conformation. In summary, compound 8 may serve as a potential dual E. coli DNA B and Topoisomerase IV inhibitor.

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Thiourea Derivatives Based on the Dapsone‐Naphthoquinone Hybrid as Anticancer and Antimicrobial Agents: In Vitro Screening and Molecular Docking Studies

ChemistrySelect ◽

10.1002/slct.201903179 ◽

2020 ◽

Vol 5 (2) ◽

pp. 847-852 ◽

Cited By ~ 2

Author(s):

Aazam Alimohammadi ◽

Hossein Mostafavi ◽

Majid Mahdavi

Keyword(s):

Molecular Docking ◽

Antimicrobial Agents ◽

Docking Studies ◽

In Vitro Screening ◽

Thiourea Derivatives ◽

Molecular Docking Studies

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Acetylcholinesterase inhibitory activity and neuroprotection in vitro, molecular docking, and improved learning and memory functions of demethylcurcumin in scopolamine-induced amnesia ICR mice

Food & Function ◽

10.1039/c9fo02339a ◽

2020 ◽

Vol 11 (3) ◽

pp. 2328-2338 ◽

Cited By ~ 1

Author(s):

Yuh-Hwa Liu ◽

Chia-Jung Lee ◽

Liang-Chieh Chen ◽

Tai-Lin Lee ◽

Ying-Ying Hsieh ◽

...

Keyword(s):

Molecular Docking ◽

Learning And Memory ◽

Inhibitory Activity ◽

Proof Of Concept ◽

Memory Functions ◽

Icr Mice ◽

Inhibitory Activities ◽

Improved Learning ◽

Concept Validation

Demethylcurcumin (DC) interventions improved learning and memory functions in scopolamine-induced amnesia ICR mice, providing the proof-of-concept validation of AChE inhibitory activities in vitro and molecular docking with AChE in silico.

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Synthesis, Urease Inhibition, Antioxidant, Antibacterial, and Molecular Docking Studies of 1,3,4-Oxadiazole Derivatives

ISRN Pharmacology ◽

10.5402/2012/928901 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 23

Author(s):

Muhammad Hanif ◽

Khurram Shoaib ◽

Muhammad Saleem ◽

Nasim Hasan Rama ◽

Sumera Zaib ◽

...

Keyword(s):

Molecular Docking ◽

Potassium Hydroxide ◽

Antioxidant Activities ◽

Docking Studies ◽

Potassium Salts ◽

Jack Bean ◽

Molecular Docking Studies ◽

Oxadiazole Derivatives ◽

Urease Inhibitory

A series of eighteen 1,3,4-oxadiazole derivatives have been synthesized by treating aromatic acid hydrazides with carbon disulfide in ethanolic potassium hydroxide yielding potassium salts of 1,3,4-oxadiazoles. Upon neutralization with 1 N hydrochloric acid yielded crude crystals of 1,3,4-oxadiazoles, which were purified by recrystallization in boiling methanol. The synthesized 1,3,4-oxadiazoles derivatives were evaluated in vitro for their urease inhibitory activities, most of the investigated compounds were potent inhibitors of Jack bean urease. The molecular docking studies were performed by docking them into the crystal structure of Jack bean urease to observe the mode of interaction of synthesized compounds. The synthesized compounds were also tested for antibacterial and antioxidant activities and some derivatives exhibited very promising results.

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Selected Derivatives of Erythromycin B-In Silico and Anti-Malarial Studies

Materials ◽

10.3390/ma14226980 ◽

2021 ◽

Vol 14 (22) ◽

pp. 6980

Author(s):

Pranab K. Bhadra ◽

Rachael N. Magwaza ◽

Niroshini Nirmalan ◽

Sally Freeman ◽

Jill Barber ◽

...

Keyword(s):

Molecular Docking ◽

In Silico ◽

Bacterial Agent ◽

Ic50 Values ◽

Exit Tunnel ◽

Erythromycin A ◽

Erythronolide B ◽

In Silico Molecular Docking ◽

Derivatives Of

Erythromycin A is an established anti-bacterial agent against Gram-positive bacteria, but it is unstable to acid. This led to an evaluation of erythromycin B and its derivatives because these have improved acid stability. These compounds were investigated for their anti-malarial activities, by their in silico molecular docking into segments of the exit tunnel of the apicoplast ribosome from Plasmodium falciparum. This is believed to be the target of the erythromycin A derivative, azithromycin, which has mild anti-malarial activity. The erythromycin B derivatives were evaluated on the multi-drug (chloroquine, pyrimethamine, and sulfadoxine)-resistant strain K1 of P. falciparum for asexual growth inhibition on asynchronous culture. The erythromycin B derivatives were identified as active in vitro inhibitors of asexual growth of P. falciparum with low micro-molar IC50 values after a 72 h cycle. 5-Desosaminyl erythronolide B ethyl succinate showed low IC50 of 68.6 µM, d-erythromycin B 86.8 µM, and erythromycin B 9-oxime 146.0 µM on the multi-drug-resistant K1 of P. falciparum. Based on the molecular docking, it seems that a small number of favourable interactions or the presence of unfavourable interactions of investigated derivatives of erythromycin B with in silico constructed segment from the exit tunnel from the apicoplast of P. falciparum is the reason for their weak in vitro anti-malarial activities.

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