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An efficient, one-pot and four-component protocol for the synthesis of new series of 2,3-disubstituted isoindolin-1-ones is performed and their Jack bean urease inhibitory activities are evaluated. All the obtained compounds 5a-p were found to be more active than the standard drugs thiourea and hydroxyurea. Molecular docking studies of these compounds were also performed that verified the results form in vitro tests. • Isoindolin-1-ones as new urease inhibitors. • Docking studies and in-silico ADME evaluation of derivatives. An efficient, one-pot and four-component synthesis of a new series of 2,3-disubstituted isoindolin-1-ones is described and their Jack bean urease inhibitory activities are evaluated. Heating a mixture of 1,1-bis(methylthio)-2-nitroethene, a 1,2-diamine, a 2-formylbenzoic acid and a primary amine in EtOH for 3.5 h afforded the corresponding 2,3-disubstituted isoindolin-1-ones in good to excellent yields. All sixteen synthesized isoindolin-1-one derivatives 5a–p showed urease inhibitory activity. Among them, 5c showed the most urease inhibitory activity (IC 50 = 10.07 ± 0.28 µM) being over 2-fold more potent than thiourea (IC 50 = 22.01 ± 0.10 µM) and 10-fold than hydroxyurea (IC 50 = 100.00 ± 0.02 µM) as the standard inhibitors, respectively. Also, results from molecular docking studies were in good agreement with those obtained from in vitro tests. [ABSTRACT FROM AUTHOR]

• A new series of 5,6-dichloro-2-methyl-1 H -benzimidazoles were synthesized. • All the compounds were evaluated for their antiurease activities. • Benzimidazole derivatives exhibited good urease inhibitor activity. • Molecular docking studies were also conducted on enzyme extracted from Jack bean urease. A novel series of 5,6-dichloro-2-methyl-1 H -benzimidazole derivatives was synthesized and then screened for their urease inhibitory activity. All compounds showed more potent inhibitory activity in the range of IC 50 = 0.0294 ± 0.0015–0.1494 ± 0.0041 µM than thiourea (IC 50 = 0.5117 ± 0.0159 µM), as a reference inhibitor. Among all the tested compounds, the compound 15 (IC 50 = 0.0294 ± 0.0015 µM) having strong electron-withdrawing nitro group on the phenyl ring was recorded as the most potent inhibitor of urease. All compounds were docked at the active sites of the Jack bean urease enzyme to investigate the reason of the inhibitory activity and the possible binding interactions of enzyme-ligand complexes. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A new series of quinazolin-4(3 H)-one derivatives was synthesized. • All the target compounds were evaluated for their antiurease activities. • Most of the compounds showed excellent inhibitory effect against urease enzyme. • Binding poses of studied compounds were determined using induced fit docking algorithms. Abstract A new series of quinazolinone derivatives containing triazole, thiadiazole, thiosemicarbazide functionalities was synthesized and then screened for their in vitro urease inhibition properties. Most of the compounds showed excellent activity with IC 50 values ranging between 1.88 ± 0.17 and 6.42 ± 0.23 µg/mL, compared to that of thiourea (IC 50 = 15.06 ± 0.68) and acetohydroxamic acid (IC 50 = 21.03 ± 0.94), as reference inhibitors. Among the synthesized molecules, compounds 5c, 5e and 5a showed the best inhibitory effect against urease enzyme with IC 50 values of 1.88 ± 0.17 µg/mL, 1.90 ± 0.10 and 1.96 ± 0.07 µg/mL, respectively. Moreover in order to give better understanding of the inhibitory activity of synthesized compounds, molecular docking studies were applied at the target sites of jack bean urease enzyme (JBU). Their binding poses and energy calculations were analyzed using induced fit docking (IFD) and prime-MMGBSA tool. Binding poses of studied compounds were determined using induced fit docking (IFD) algorithms. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Biology-oriented drug synthesis (BIODS) of S -naproxen derivatives 1 – 39. • Structural characterization of compounds by various spectroscopic techniques. • Evaluation of compounds 1 – 39 for in vitro urease inhibitory activity. • Possible structure-activity relationship (SAR). • Assessment of binding interactions of compounds with the active site of urease enzyme by the molecular docking study. Abstract Current study is based on the biology-oriented drug synthesis (BIODS) of S -naproxen (NSAID) derivatives and the evaluation of their urease inhibitory potential. In this regard, a variety of S -naproxen derivatives 2 – 39 including hydrazide 1 , Schiff bases 2 – 21 , aroyl substituted hydrazides 22 – 24 , sulfohydrazides 25 – 34 , 2-mercapto oxadiazole 35 , phenacyl substituted 2-mercapto oxadiazoles 36 – 39 were synthesized under the umbrella of BIODS by simple chemical transformation of its pharmacophoric carboxylic group. Compounds 1 – 39 were evaluated for in vitro urease inhibitory activity and most of them showed good to moderate inhibitory potential in the range of IC 50 = 14.01 ± 0.23–76.43 ± 0.8 µM as compared to standard acetohydroxamic acid (IC 50 = 27.0 ± 0.5 µM). Limited structure-activity relationship (SAR) was established in order to rationalize the participation of varying groups (R) in the inhibitory potential of compounds. Molecular docking study on all active compounds was also carried out to decipher the interactions detail of the ligand with the receptors of active site of enzyme. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Synthesis of acridine-based (thio)semicarbazones and hydrazones. • Screening as urease inhibitors. • Molecular docking and in-silico ADME evaluation. Abstract Urease is a bacterial enzyme that is responsible for virulence of various pathogenic bacteria such as Staphylococcus aureus, Proteus mirabilis , Klebsiella pneumoniae , Ureaplasma urealyticum , Helicobacter pylori and Mycobacterium tuberculosis. Increased urease activity aids in survival and colonization of pathogenic bacteria causing several disorders especially gastric ulceration. Hence, urease inhibitors are used for treatment of such diseases. In search of new molecules with better urease inhibitory activity, herein we report a series of acridine derived (thio)semicarbazones (4a-4e , 6a-6l) that were found to be active against urease enzyme. Molecular docking studies were carried out to better comprehend the preferential mode of binding of these compounds against urease enzyme. Docking against urease from pathogenic bacterium S. pasteurii was also carried out with favorable results. In silico ADME evaluation was done to determine drug likeness of synthesized compounds. [ABSTRACT FROM AUTHOR]

A new series of 2,3-disubstituted quinazolin-4(3 H )-one compounds including oxadiazole and furan rings was synthesized. Their inhibitory activities on urease were assessed in vitro . All newly synthesized compounds exhibited potent urease inhibitory activity in the range of IC 50  = 1.55 ± 0.07–2.65 ± 0.08 µg/mL, when compared with the standard urease inhibitors such as thiourea (IC 50  = 15.08 ± 0.71 µg/mL) and acetohydroxamic acid (IC 50  = 21.05 ± 0.96 µg/mL). 2,3-Disubstituted quinazolin-4(3 H )-one derivatives containing furan ring ( 3a-e ) were found to be the most active inhibitors when compared with the compounds 2a-e bearing oxadiazole ring. Compound 3a, bearing 4-chloro group on phenyl ring, was found as the most effective inhibitor of urease with the IC 50 value of 1.55 ± 0.11 µg/mL. The molecular docking studies of the newly synthesized compounds were performed to identify the probable binding modes in the active site of the Jack bean urease (JBU) enzymes. [ABSTRACT FROM AUTHOR]

Nicotinic and isonicotinic thiosemicarbazide or hydrazine carbothioamides 3 – 27 were synthesized and the structures of synthetic compounds were elucidated by various spectroscopic techniques such as EI-MS, 1 H-, and 13 C NMR. Synthetic derivatives were evaluated for their urease inhibitory activity which revealed that except few all derivatives demonstrated excellent inhibition in the range of IC 50 values of 1.21–51.42 μM as compared to the standard thiourea (IC 50  = 21.25 ± 0.13 μM). Among the twenty-five synthetic derivatives nineteen 1 – 5 , 7 , 8 , 10 , 12 , 14 – 18 , 20 – 22 , 24 – 27 were found to be more active showing IC 50 values between 1.13 and 19.74 μM showing superior activity than the standard. Limited structure-activity relationship demonstrated that the positions of substituent as well as position of nitrogen in pyridine ring are very important for inhibitory activity of this class of compound. To verify these interpretations, in silico study was also performed. A good correlation was obtained between the biological evaluation of active compounds and docking study. [ABSTRACT FROM AUTHOR]

A series of hydrazinecarboxamide derivatives were synthesized and examined against urease for their inhibitory activity. Among the series, the 1-(3-fluorobenzylidene)semicarbazide ( 4a ) (IC 50  = 0.52 ± 0.45 µM), 4u (IC 50  = 1.23 ± 0.32 µM) and 4h (IC 50  = 2.22 ± 0.32 µM) were found most potent. Furthermore, the molecular docking study was also performed to demonstrate the binding mode of the active hydrazinecarboxamide with the enzyme, urease. In order to estimate drug likeness of compounds, in silico ADME evaluation was carried out. All compounds exhibited favorable ADME profiles with good predicted oral bioavailability. [ABSTRACT FROM AUTHOR]

Urease is known to be one of the major causes of diseases induced by Helicobacter pylori , thus allow them to survive at low pH inside the stomach and thereby, play an important role in the pathogenesis of gastric and peptic ulcer, apart from cancer as well. Keeping in view the great importance of urease inhibitors, here in this study we have synthesized piperazine derivatives ( 1 – 15 ) and evaluated for their urease inhibitory activity. All analogs showed excellent inhibitory potential with IC 50 values ranging between 1.1 ± 0.01 and 33.40 ± 1.50 µM when compared with the standard inhibitor thiourea (IC 50  = 21.30 ± 1.10 µM). Structure activity relationship has been established for all compounds which are mainly based upon the substitution on phenyl ring. Molecular docking study was performed in order to understand the binding interaction of the compounds in the active site of enzyme. [ABSTRACT FROM AUTHOR]

3,4-Dimethoxybenzohydrazide derivatives ( 1–25 ) have been synthesized and evaluated for their urease inhibitory potential. Among the series, compounds 2 , 3 , 4 and 5 with IC 50 values 12.61 ± 0.07, 18.24 ± 0.14, 19.22 ± 0.21, and 8.40 ± 0.05 µM, respectively, showed excellent urease inhibitory potentials when compared with standard thiourea (IC 50 value 21.40 ± 0.21 µM). Compounds 1 , 6 , 8 , 18 , 19 and 20 also showed good to moderate inhibition, while the remaining compounds were found to be completely inactive. The structures of compounds 6 and 25 were confirmed through X-ray crystallography while the structures of remaining compounds were confirmed through ESI-MS and 1 H NMR. Molecular docking studies were performed understand the binding interactions with enzyme active site. The synthesized compounds were evaluated for cytotoxicity and found to be nontoxic. [ABSTRACT FROM AUTHOR]

Sixteen 4-hydroxycoumarin derivatives were synthesized, characterized through EI-MS and 1 H NMR and screened for urease inhibitory potential. Three compounds exhibited better urease inhibition than the standard inhibitor thiourea (IC 50 = 21 ± 0.11 μM) while other four compounds exhibited good to moderate inhibition with IC 50 values between 29.45 ± 1.1 μM and 69.53 ± 0.9 μM. Structure activity relationship was established on the basis of molecular docking studies, which helped to predict the binding interactions of the most active compounds. [ABSTRACT FROM AUTHOR]

Four series of heterocyclic compounds 4-dihydropyrimidine-2-thiones 7 – 12 (series A), N , S -dimethyl-dihydropyrimidines 13 – 18 (series B), hydrazine derivatives of dihydropyrimidine 19 – 24 (series C), and tetrazolo dihydropyrimidine derivatives 25 – 30 (series D), were synthesized and evaluated for in vitro urease inhibitory activity. The series B–D were first time examined for urease inhibition. Series A and C were found to be significantly active with IC 50 values between 34.7–42.9 and 15.0–26.0 μM, respectively. The structure–activity relationship showed that the free S atom and hydrazine moiety are the key pharmacophores against urease enzyme. The kinetic studies of the active series A ( 7 – 12 ) and C ( 19 – 24 ) were carried out to determine their modes of inhibition and dissociation constants K i . Compounds of series A ( 7 – 12 ) and series C ( 19 – 24 ) showed a mixed-type of inhibition with K i values ranging between 15.76–25.66 and 14.63–29.42 μM, respectively. The molecular docking results showed that all the active compounds of both series have significant binding interactions with the active sites specially Ni-ion of the urease enzyme. Cytotoxicity of all series A–D was also evaluated against mammalian mouse fibroblast 3T3 cell lines, and no toxicity was observed in cellular model. [ABSTRACT FROM AUTHOR]

4-Thiazolidinone analogs 1–20 were synthesized, characterized by 1 H NMR and EI–MS and investigated for urease inhibitory activity. All twenty (20) analogs exhibited varied degree of urease inhibitory potential with IC 50 values 1.73–69.65 μM, if compared with standard thiourea having IC 50 value of 21.25 ± 0.15 μM. Among the series, eight derivatives 3 , 6 , 8 , 10 , 15 , 17 , 19 , and 20 showed outstanding urease inhibitory potential with IC 50 values of 9.34 ± 0.02, 14.62 ± 0.03, 8.43 ± 0.01, 7.3 ± 0.04, 2.31 ± 0.002, 5.75 ± 0.003, 8.81 ± 0.005, and 1.73 ± 0.001 μM, respectively, which is better than the standard thiourea. The remaining analogs showed good to excellent urease inhibition. The binding interactions of these compounds were confirmed through molecular docking studies. [ABSTRACT FROM AUTHOR]

Highlights: [•] A series of ethyl 4-(3-benzoylthioureido) benzoates derivative were synthesized. [•] Their urease inhibitory and antioxidant activities were evaluated. [•] Tested compounds displayed potential antiurease and antioxidant activities, and can be optimized for antiulcer drugs. [ABSTRACT FROM AUTHOR]

[Display omitted] • Design and synthesis of novel adamantane-naphthyl thiourea conjugate. • X-ray single crystal structure. • Surface and structure analysis by Hirshfeld and DFT studies. • Exploration of DNA binding, urease inhibition and anticancer activities. 1-(adamantane-1-carbonyl-3-(1-naphthyl)) thiourea (C 22 H 24 N 2 OS (4), was synthesized by the reaction of freshly prepared adamantane-1-carbonyl chloride from corresponding acid (3) with ammonium thiocyanate in 1:1 M ratio in dry acetone to afford the adamantane-1-carbonyl isothiocyanate (2) in situ followed by treatment with 1-naphthyl amine (3). The structure was established by elemental analyses, FTIR, 1H, 13C NMR and mass spectroscopy. The molecular and crystal structure were determined by single crystal X-ray analysis. It belongs to triclinic system P − 1 space group with a = 6.7832(5) Å, b = 11.1810(8) Å, c = 13.6660(10) Å, α = 105.941(6)°, β = 103.730(6)°, γ = 104.562(6)°, Z = 2, V = 910.82(11) Å3. The naphthyl group is almost planar. In the crystal structure, intermolecular C H···O hydrogen bonds link the molecules into centrosymmetric dimers, enclosing R 2 2(14) ring motifs, while the intramolecular N H···O hydrogen bonds enclose S(6) ring motifs, in which they may be effective in the stabilization of the structure. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H ... H (59.3%), H ... C/C ... H (19.8%) and H ... S/S ... H (10.1%) interactions. Hydrogen bonding and van der Waals interactions are the dominant interactions in the crystal packing. DFT, molecular docking and urease inhibition studies revealed stability and electron withdrawing nature of 4 as compared to DNA base pairs and residues of urease. The DNA binding results from docking, UV– visible spectroscopy, and viscosity studies indicated significant binding of 4 with the DNA via intercalation and groove binding. Further investigation of the compound was done on hepatocellular carcinoma; Huh-7 cell line as well as normal human embryonic kidney; Hek-293 cell line. The compound showed significant cytotoxic activity against Huh-7 cells in comparison to normal Hek-293 cells indicating selective cytotoxicity towards cancer cells. [ABSTRACT FROM AUTHOR]

• New hydrazonothiazolines (3a-3v) were synthesized via cyclization of the appropriate thiosemicarbzaone. • Single crystal X-ray crystallography was performed for compounds 3n and 3v. • All compounds displayed potent urease inhibitory activity with IC 50 values of 1.73–27.3 µM. • Structure-activity relationship was interpretatively discussed for all compounds. • Molecular docking studies were established to elucidate the binding energy and interaction. A series of new hydrazonothiazolines (3a-v) was obtained in good to excellent yields (79–96%) via cyclization of the appropriate thiosemicarbazones with phenacyl bromide. The targeted compounds were characterized by advanced spectroscopic techniques, such as FTIR, 1HNMR, 13CNMR and ESI-MS. The structure of compounds 3n and 3v was unambiguously confirmed by single crystal X-ray analysis. All compounds displayed enhanced inhibitory activity against urease enzyme with IC 50 values in range of 1.73 ± 1.57–27.3 ± 0.655 μM when compared to standard thiourea (IC 50 = 20.8 ± 0.75 µM). The structure-activity relationship studies demonstrated that the activity of this series is due the central thiazole ring that interacts with nickel atoms in the active site of urease enzyme. Moreover, molecular docking studies were carried out to investigate the binding mode of all active compounds and an inactive (3u) with the active site of the urease enzyme. The docking results are in complete agreement with the experimental finding. [ABSTRACT FROM AUTHOR]

Synthesis of (1 – 18) hybrid bis-coumarin with thiadiazole as a new inhibitor of Urease. • Synthesis of hybrid bis-coumarin. • In vitro Urease activity. • Identification of a new class of Urease activity. • Structure activity relationship established. • Molecular docking. Hybrid bis - coumarin derivatives 1 – 18 were synthesized and evaluated for their in vitro urease inhibitory potential. All compounds showed outstanding urease inhibitory potential with IC 50 value (The half maximal inhibitory concentration) ranging in between 0.12 SD 0.01 and 38.04 SD 0.63 µM (SD standard deviation). When compared with the standard thiourea (IC 50 = 21.40 ± 0.21 µM). Among these derivatives, compounds 7 (IC 50 = 0.29 ± 0.01), 9 (IC 50 = 2.4 ± 0.05), 10 (IC 50 = 2.25 ± 0.05) and 16 (IC 50 = 0.12 ± 0.01) are better inhibitors of the urease compared with thiourea (IC 50 = 21.40 ± 0.21 µM). To find structure–activity relationship molecular docking as well as absorption, distribution, metabolism, and excretion (ADME) studies were also performed. Various spectroscopic techniques like 1H NMR, 13C NMR, and EI-MS were used for characterization of all synthesized analogs. All compounds were tested for cytotoxicity and found non-toxic. [ABSTRACT FROM AUTHOR]