scholarly journals Bio-oriented synthesis of new sulphadiazine derivatives for urease inhibition and their pharmacokinetic analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Asad Hamad ◽  
Mohsin Abbas Khan ◽  
Irshad Ahmad ◽  
Ruqaiya Khalil ◽  
Muhammad Khalid ◽  
...  
Keyword(s):  
Aromatic Aldehydes ◽  
Docking Studies ◽  
Pharmacokinetic Analysis ◽  
Spectroscopic Techniques ◽  
Urease Enzyme ◽  
Urease Inhibitory ◽  
Hydroxy Groups ◽  
By Products

AbstractCurrent research is based on biology-oriented synthesis of sulphadiazine derivatives and determination of their urease inhibitory activity. In this regard, a series of (E)-4-(benzylideneamino)-N-(pyrimidin-2-yl)benzenesulfonamide was synthesized from sulphadiazine and substituted aromatic aldehydes. The structures of synthesized compounds were ascertained by spectroscopic techniques, such as, FTIR, NMR and HRMS analysis, and in-vitro and in-silico investigation were carried out for the inhibition of urease. Ureases are harmful for humans by producing by-products of urea (ammonia and carbon dioxide). The most active compound (3l) against urease exhibited IC50 value of 2.21 ± 0.45 µM which is 10 times more potent than the standard thiourea (20.03 ± 2.06 µM). It is noteworthy that most of our synthesized compounds showed significant to excellent activities against urease enzyme and most of them substituted by halogen or hydroxy groups at ortho and para positions in their structures. Inhibition of enzyme by the synthesized analogues was in descending order as 3l > 3a > 3b > 3q > 3e > 3o > 3s > 3t > 3g > 3k > 3r > 3f > 3m > 3p > 3n > 3j > 3i > 3h. Moreover, molecular docking studies were performed to rationalize the binding interactions of the synthesized motifs with the active pocket of the urease enzyme. The synthesized sulphadiazine derivatives (3a–u) were found to be non-toxic, and presented passive gastrointestinal absorption.

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

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.

scholarly journals A new series of 2,4-thiazolidinediones endowed with potent aldose reductase inhibitory activity

2021 ◽  
Vol 19 (1) ◽  
pp. 347-357
Author(s):  
Belgin Sever ◽  
Mehlika Dilek Altıntop ◽  
Yeliz Demir ◽  
Cüneyt Türkeş ◽  
Kaan Özbaş ◽  
...  
Keyword(s):  
Aldose Reductase ◽  
In Silico ◽  
Aromatic Aldehydes ◽  
Docking Studies ◽  
Mouse Fibroblast ◽  
L929 Mouse Fibroblast ◽  
Orally Bioavailable ◽  
L929 Mouse ◽  
Solvent Free Reaction

Abstract In an effort to identify potent aldose reductase (AR) inhibitors, 5-(arylidene)thiazolidine-2,4-diones (1–8), which were prepared by the solvent-free reaction of 2,4-thiazolidinedione with aromatic aldehydes in the presence of urea, were examined for their in vitro AR inhibitory activities and cytotoxicity. 5-(2-Hydroxy-3-methylbenzylidene)thiazolidine-2,4-dione (3) was the most potent AR inhibitor in this series, exerting uncompetitive inhibition with a K i value of 0.445 ± 0.013 µM. The IC50 value of compound 3 for L929 mouse fibroblast cells was determined as 8.9 ± 0.66 µM, pointing out its safety as an AR inhibitor. Molecular docking studies suggested that compound 3 exhibited good affinity to the binding site of AR (PDB ID: 4JIR). Based upon in silico absorption, distribution, metabolism, and excretion data, the compound is predicted to have favorable pharmacokinetic features. Taking into account the in silico and in vitro data, compound 3 stands out as a potential orally bioavailable AR inhibitor for the management of diabetic complications as well as nondiabetic diseases.

scholarly journals SYNTHESIS AND ANTIMALARIAL ACTIVITY OF SOME NEW 3-PHENYL-2-THIOXOTHIAZOLIDIN-4-ONE DERIVATIVES

2017 ◽  
Vol 9 (3) ◽  
pp. 58
Author(s):  
Mehul Zaveri ◽  
Neha Kawathekar
Keyword(s):  
Antimalarial Activity ◽  
Research Work ◽  
Aromatic Aldehydes ◽  
Maximum Activity ◽  
Spectroscopic Techniques ◽  
Activity Data ◽  
Antimalarial Agents ◽  
Ic50 Values ◽  
Current Therapies

Objective: Current therapies to treat P. falciparum malaria are heavily reliant on artemisinin-based combinations. However, resistance to artemisinin has recently been identified, and resistance to key artemisinin partner drugs is already widespread. Therefore, there is an urgent need for new antimalarial drugs with improved attributes over older therapies. The objective of this research work is to synthesize new antimalarial agents more effective against clinically relevant malarial strains.Methods: In present work, a series of ten 3-phenyl-2-thioxothiazolidin-4-one (MF1-MF10) derivatives, were synthesized by Knoevenagel condensation of N-phenyl rhodanine (I1) with substituted aromatic or hetro aromatic aldehydes using microwave irradiation. N-phenyl rhodanine (I1) was synthesized by a conventional reaction involving methyl-2-mercaptoacetate (1) and phenyl Isothiocyanates in presence of triethylamine. All the synthesized compounds were characterized by various spectroscopic techniques and evaluated for in-vitro antimalarial activity by microdilution technique against resistance strains of Plasmodium falciparum.Results: The antimalarial activity data showed that six compounds (MF1, MF3, MF4, MF5, MF7 and MF8) exhibited IC50 values ranging from 1.0-1.30 µg/ml, three compounds (MF2, MF6 and MF10) displayed IC50 values in the range of 0.9-1.0 µg/ml. Compound MF9 showed most significant result with maximum activity (IC50 = 0.85µg/ml).Conclusion: The antimalarial activity results revealed that compound MF9 possess potent activity and could be identified as a promising lead for further investigation.

scholarly journals Synthesis, antimalarial activity evaluation and molecular docking studies of some novel dispiro-1,2,4,5-tetraoxanes

2015 ◽  
Vol 10 (4) ◽  
pp. 917 ◽  
Author(s):  
Mukesh Kumar Kumawat ◽  
Dipak Chetia
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Docking ◽  
Resistant Strain ◽  
Antimalarial Activity ◽  
Binding Pocket ◽  
Docking Studies ◽  
Spectroscopic Techniques ◽  
Molecular Docking Studies ◽  
Activity Screening

<p class="Abstract">Seven novel dispiro-1,2,4,5-tetraoxane derivatives were synthesized and characterized by a number of analytical and spectroscopic techniques. The molecules were subsequently screened for in vitro antimalarial activity against chloroquine resistant strain of <em>Plasmodium falciparum</em> (RKL-9). At antimalarial activity screening, two compounds, namely 5d (MIC = 15.6 µg/mL or 64.5 µM) and 5f (MIC = 15.6 µg/mL or 54.6 µM) were found to be about 1.5 times more potent against chloroquine resistant strain-RKL-9 compared to chloroquine (MIC = 25.0 µg/mL or 78.3 µM). Molecular docking studies of potent ligands were also performed in cysteine protease binding pocket residues of falcipain-2 as a target protein.</p><p> </p>

Investigation of tyrosinase inhibition by some 1,2,4 triazole derivative compounds: in vitro and in silico mechanisms

2018 ◽  
Vol 44 (4) ◽  
pp. 473-481
Author(s):  
Elif Ayazoglu Demir ◽  
Ahmet Colak ◽  
Aylin Kalfa ◽  
Ahmet Yasar ◽  
Olcay Bekircan ◽  
...  
Keyword(s):  
Critical Role ◽  
Docking Studies ◽  
Biosynthesis Pathway ◽  
Mushroom Tyrosinase ◽  
Tyrosinase Inhibitor ◽  
Effective Inhibitor ◽  
Tyrosinase Inhibition ◽  
Triazole Derivative

Abstract Background Tyrosinase plays a central role in the biosynthesis pathway of melanin pigment. Melanin protects human skin against radiation and its unusual levels cause some skin disorders such as pregnancy scar, oldness spots and melanoma. Tyrosinase has also been linked to Parkinson’s and other neurodegenerative diseases. In addition, melanin plays a critical role as a defense molecule for insects during wound healing and is important for their life. Therefore, determination of inhibitor molecules for tyrosinase has a promising potential for therapies of some diseases and is an alternative method for keeping insects under control. Material and methods In this study, 1-hepthyl-3-(4-methoxybenzyl)-4H-1,2,4-triazole-5-one derivative (A6, A8, A15) and 3-(4-chlorophenyl)- 5-(4-methoxybenzyl)-4H-1,2,4-triazole (B5, B9, B13) derivative compounds were evaluated in terms of their potential for mushroom tyrosinase inhibition. IC50 values of these six molecules were determined. Results It was seen that B9 molecule was the most effective inhibitor. Docking studies also nearly supported this end result. Tyrosinase inhibition type and Ki value were found to be uncompetitive and 370.7±0.3 μM, respectively, in the presence of B9 compound. Conclusion These results suggest that B9 compound is a potential tyrosinase inhibitor.

THEVETIA PERUVIANA ROOTS EXTRACT MEDICATED GOLD NANOPARTICLES AND ITS UREASE INHIBITORY ACTIVITY

2021 ◽  
pp. 79-82
Author(s):  
SAUD BAWAZEER
Keyword(s):  
Gold Nanoparticles ◽  
Aqueous Extract ◽  
Inhibitory Activity ◽  
Enzyme Inhibitor ◽  
Research Work ◽  
Thevetia Peruviana ◽  
Urease Enzyme ◽  
Urease Inhibitory ◽  
Microscopy Techniques

Objective: The main objective of the current research work was synthesized of gold nanoparticles (AuNPs) of Thevetia peruviana aqueous extract,characterization, and screening for urease enzyme inhibitory activity.Methods: AuNPs were synthesized by mixing 1 mM gold salt solution with T. peruviana aqueous extract without any reducing agents. The preparedAuNPs were characterized using UV–visible spectroscopy, Fourier transform infrared spectroscopy, and scanning electron microscopy techniques. Thesynthesized AuNPs were assessed for in vitro urease enzyme inhibitory activity at 0.2 μg in comparison with the aqueous extract.Results: In this finding, we synthesized the AuNPs of T. peruviana aqueous extract for the 1st time. The AuNPs exhibited significant stability atroom temperature. The AuNPs showed significant urease inhibitory activity with IC50 67.56±1.67 at 0.2 μg as compared to aqueous extract whichexhibited good activity with IC50 39.21±1.32 μ at 0.2 mg, against standard thiourea (IC50=21.00±1.16). The formation of AuNPs correlates due to activephytochemical present in extract which is responsible for synthesizing NPs.Conclusion: T. peruviana extract and prepared AuNPs are an outstanding urease enzyme inhibitor and are capable of making fine NPs. Application:The synthesized AuNPs of T. peruviana aqueous extract which significant urease inhibitory activity may allow us to discover NPs for potentiallyeffective and safe nanoherbal therapy.

scholarly journals Kinase Inhibitors of Novel Pyridopyrimidinone Candidates: Synthesis and In Vitro Anticancer Properties

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Nagy M. Khalifa ◽  
Mohamed A. Al-Omar ◽  
Hamad M. Alkahtani ◽  
Ahmed H. Bakheit
Keyword(s):  
Kinase Inhibitors ◽  
Human Cancer ◽  
Ethyl Cyanoacetate ◽  
Diethyl Malonate ◽  
Aromatic Aldehydes ◽  
Docking Studies ◽  
Braf V600e ◽  
Kinase Assay ◽  
Human Cancer Cell Lines

A new class of pyridopyrimidinone compounds containing different nitrogenous heterocycles were synthesized starting from the key precursor 2-hydrazinyl-5-phenyl-7-(pyridin-3-yl)pyrido[2,3-d]pyrimidin-4(3H)-one via condensation with series of aromatic aldehydes and cyclization using different reagents as ethyl acetoacetate, ethyl cyanoacetate, diethyl malonate, and ammonium isothiocyanate. The bioassay results showed compound 6 to be highly effective towards three human cancer cell lines (HepG2, PC-3, and HCT-116) in vitro with promising activity values (IC50: 0.5 μM) relative to the standard doxorubicin (IC50: 0.6 μM). Kinase inhibitory evaluation of compound 6 displays hopeful inhibitory action against BRAF V600E, EGFR, and PDGFRβ at100 μM. The molecular docking studies supported the initial kinase assay.

scholarly journals α-Glucosidase Inhibition and Molecular Docking Studies of Natural Brominated Metabolites from Marine Macro Brown Alga Dictyopteris hoytii

Marine Drugs ◽  
2019 ◽  
Vol 17 (12) ◽  
pp. 666 ◽  
Author(s):  
Najeeb Ur Rehman ◽  
Kashif Rafiq ◽  
Ajmal Khan ◽  
Sobia Ahsan Halim ◽  
Liaqat Ali ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Brown Alga ◽  
Docking Studies ◽  
Spectroscopic Techniques ◽  
Molecular Docking Studies ◽  
Ethyl Methyl ◽  
2D Noesy ◽  
Ic50 Value ◽  
Ic50 Values

Bioassay guided isolation of the methanolic extract of marine macro brown alga Dictyopteris hoytii afforded one new metabolite (ethyl methyl 2-bromobenzene 1,4-dioate, 1), one new natural metabolite (diethyl-2-bromobenzene 1,4-dioate, 2) along with six known metabolites (3–8) reported for the first time from this source. The structure elucidation of all these compounds was achieved by extensive spectroscopic techniques including 1D (1H and 13C) and 2D (NOESY, COSY, HMBC and HSQC) NMR and mass spectrometry and comparison of the spectral data of known compounds with those reported in literature. The in vitro α-glucosidase inhibition studies confirmed compound 7 to be the most active against α-glucosidase enzyme with IC50 value of 30.5 ± 0.41 μM. Compounds 2 and 3 demonstrated good inhibition with IC50 values of 234.2 ± 4.18 and 289.4 ± 4.91 μM, respectively, while compounds 1, 5, and 6 showed moderate to low inhibition. Furthermore, the molecular docking studies of the active compounds were performed to examine their mode of inhibition in the binding site of the α-glucosidase enzyme.

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

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
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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