Urease Inhibitory Activity Research Articles

Synthesis, Characterization and Crystal Structures of Thiosemicarbazones with Urease Inhibitory Activity

Synthesis, Characterization and Crystal Structures of Thiosemicarbazones with Urease Inhibitory Activity

Synthesis and Characterization of New Bistriazole Quinazolinediones and their Urease Inhibition Activities

Abstract: A new series of bisthiosemicarbazide and bistriazole molecules bridged quinazolinedione was synthesized and characterized by FT-IR, 1 H and 13C-NMR spectral data. Antiurease activities of all new compounds were tested according to the phenol-hypochlorite method by Weatherburn. All compounds have effective urease inhibition activities compared to the standard inhibitor thiourea and previously synthesized quinazolinones as potential inhibitors. Bistriazoles containing quinazolinedione have the best inhibition results. 1,3-Bis[(4-ethyl-5-mercapto-4H-1,2,4-triazol-3-yl)methyl]quinazoline2,4(1H,3H)-dione (5b) has the best inhibitory activity with 1.25 ± 0.45 µg/mL IC50 value.

Phytochemical Profiling, in Vitro Biological Activities and in Silico Molecular Docking Studies of the Crude Extract of Crambe orientalis, an Endemic Plant in Turkey.

In this study, total phenolic and flavonoid analyses of flower, leaf, and stem aqueous extracts of C. orientalis were performed. Total phenolic contents of C. orientalis extracts ranged from 12.2±0.06 to 19.0±0.07 mg GAE/g extract. Total flavonoid values range between 2.0±0.11 and 6.6±0.19 mg CE/g extract. Urease, collagenase, tyrosinase, and α-glucosidase inhibition activities were determined in vitro and the relationship between them was examined. IC50 results for all enzymes were obtained between 0.18 and 3.53 μg/mL. The aqueous extract of the plant C. orientalis showed potent cytotoxic effects against the human colon cancer cell lines DLD-1. As the extract concentration increases, cell death increases. The main fatty acid composition by GC/MS analysis is erucic acid (36.5 %). The potential binding modes of the fatty acids in the plant extract to the enzymes and possible inhibition mechanisms were determined by molecular docking calculation.

Cholinesterase, α-glucosidase, tyrosinase and urease inhibitory activities of compounds from fruits of Rinorea oblongifolia C.H. Wright (Violaceae)

From Rinorea oblongifolia fruits, 3-Nor-4β-friedelan-24-ol (1) and 3-decyl-6,7,8-trimethoxy-2H,5H-furo[4,3,2-de]isochromene-2,5-dione (4), new derivatives alongside, 28-hydroxyfriedelan-3-one (2), friedelin (3), 3,3’,4,4’,5’-pentamethylcoruleoellagic acid (5), hexamethylcoruleoellagic acid (6), 3’,4,4’,5,5’-pentamethylcoruleoellagic acid (7), and fatty compounds 8-11 were isolated and characterized using HRESIMS, EIMS, 1D and 2D NMR. In vitro enzyme inhibition of compounds 1, 2, 4, 5, 6 and 7 were evaluated on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-glucosidase, urease and tyrosinase. Against AChE and BChE, the phenolic compounds 4, 5, 6, and 7 had good activity probably due to the phenolic nature and methoxy substituents. Compounds 4, 5, 6 and 7 exhibited good α-glucosidase inhibition especially compound 4 whose IC50 = 42.45 ± 0.46 µg/mL was close that of acarbose (IC50 = 20.52 ± 0.84 µg/mL) standard drug. Urease and tyrosinase were appreciably inhibited by the compounds. Overall results of enzyme inhibitory assays indicate Rinorea oblongifolia, fruits and its constituents as potential remedy for enzymatic disorders.

Urease inhibitory activity on 1,2,3-triazoles-linked indomethacin derivatives; in vitro and in silico studies

The current research is based on the biology-oriented drug synthesis (BIODS) approach for synthesizing 1,2,3-triazoles-linked indomethacin derivatives (5–20). The multi-step synthesis from indomethacin (1) under base-catalyzed conditions afforded propargyl ester (2), which was further reacted with substituted azides (4a-p) of acetophenone (3a-p) to afford corresponding 1,2,3-triazole derivatives (5–20) in excellent yields. Structures of all synthetic derivatives were elucidated through various spectroscopic techniques such as UV, IR, EI-MS, HR-MS, 1H NMR, 13C NMR, and 2D-NMR. All compounds 5–20 were evaluated for their inhibitory potential against the urease enzyme, which showed good inhibition in the range of IC50 = 21.7 ± 0.28 - 89.5 ± 0.34 μM compared to the standard thiourea (IC50 = 22.4 ± 0.29 μM). Compounds 5 (IC50 = 22.8 ± 0.78 μM), 10 (IC50 = 22.8 ± 0.78 μM), and 18 (IC50 = 21.7 ± 0.28 μM) were found to be most active and could serve as an attractive building block in the search for novel urease inhibitors. To ensure the accuracy of these interpretations, in silico analysis was also carried out. The results showed a strong correlation between the bioactivities and the docking investigations.

Efecto anti-ureasa y actividad antibacteriana del extracto de raíz de Cylindropuntia cholla

In this study, the root extract of Cylindropuntia cholla was analyzed as a possible source of substances with potential urease inhibitory and antibacterial activity. C. cholla cactus are abundant in the arid regions of Mexico and are traditionally used to treat kidney diseases, urinary tract infections, and in some cases, to combat the formation of kidney stones. Anti-urease action was evaluated from methanolic root extracts by initial velocity methods. We observed an IC50 of 2.04 mg/mL. Lineweaver-Burk pattern showed an uncompetitive inhibition. The antibacterial activity was evaluated over Klebsiella pneumoniae (ATCCTM 13883) and Staphylococcus aureus (ATCCTM 25923) and we only observed effects over S. aureus growth at 200 mg/mL of extract concentration.

SYNTHESIS, CHARACTERIZATION AND CRYSTAL STRUCTURES OF THIOSEMICARBAZONES WITH UREASE INHIBITORY ACTIVITY

Thiosemicarbazones are biological active compounds. In this work, five new thiosemicarbazones were prepared and structurally characterized by elemental analysis, 1H NMR and IR spectra, as well as single crystal X-ray diffraction. The compounds were evaluated for their urease inhibitory activities. Among the compounds, those with hydroxyl substituent groups have effective activity with IC50 values of 1.5-2.3 μmol∙L–1. Docking simulation was performed to insert the molecules of the compounds into the crystal structure of Jack bean urease at the active site to determine their probable binding modes.

GC-MS Analysis and Biological Effects of Essential Oil from Trachyspermum ammi L

Trachyspermum ammi L, local seed’s essential oil and its crude methanolic extract were evaluated for antioxidant, antibacterial, and urease inhibition activities. Largely, 18 constituents were identified in the essential oil using The GC-MS. The promising constituent reported was terpeniodes; which seem to be responsible for the reported biological activities. DPPH Free radica1 scavenging assay was done to evaluate the antioxidant activities of both oil and crude extract. The DPPH scavenging activity results in lC50 values of 75 and#177; 0.05 and 300 and#177; 0.03. Antibacterial activity of the oil was carried out by using strains of Escherichia coli (89%), Bacillus subtilis (85%), and Streptococcus aureus (80%), while for the crude extract strains of E. coli (86%) B. subtle (89%), and S. aureus; (85%) were used. E. coil of T. ammi exhibits promising results with Aspergillus. flavus1 (86%) and Aspergillus1 Niger1 (87%). The phytochemical analysis of the T. ammi, crude extract showed the presence of saponins, flavonoids, steroids, terpenoids, and cardiac glycosides in the phytochemical investigation. Urease inhibition showed potent inhibition against B.P and J.B Urease with IC50 values of 85 and#177; 0.06 and 67.45 and#177; 0.8, respectively. Plant crude showed optimal results for B.P and Jack bean urease with IC50 values of 55.77 and#177; 0.01 and 35.56 and#177; 0.04, respectively.

Novel flurbiprofen clubbed oxadiazole derivatives as potential urease inhibitors and their molecular docking study.

In this study, twenty eight novel oxadiazole derivatives (5-32) of the marketed available non-steroidal anti-inflammatory drug (NSAID), (S)-flurbiprofen (1), were synthesized via I2 mediated cyclo-addition reaction in better yields. The synthesized hydrazone-Schiff bases were cyclized with iodine by using potassium hydroxide as a base in DMSO solvent to obtain oxadiazole derivatives (5-32). Structures of the synthesized products were confirmed with HR-ESI-MS, 1H-NMR spectroscopy and CHN analysis. After structure confirmations all analogs were evaluated for urease (in vitro) inhibitory activity. Amongst the series, fourteen compounds 20, 26, 30, 24, 21, 16, 28, 31, 32, 7, 19, 13, 10, and 6 were found to be excellent inhibitors of urease enzyme, having IC50 values of 12 ± 0.9 to 20 ± 0.5 μM, better than the standard thiourea (IC50 = 22 ± 2.2 μM), whereas the remaining fourteen derivatives displayed good to moderate activity. The in silico study was executed to analyse the interaction between the active site of the enzyme (urease) and the produced compounds. The docking study revealed that compounds 20, 26, 30, 24, 21, 16, 28, 31, 32, 7, 19, 13, 10, and 6 had lower docking scores than the standard compound thiourea and revealed better interactions with the urease enzyme.

Combined experimental and computational approach toward biological, physicochemical and quantum chemical aspects of substituted 1-[5-phenyl-3-(2-trifluoromethyl-phenyl)-4,5-dihydro-pyrazol-1-yl]-ethanone

In current work, three N-acetyl pyrazoline derivatives (1–3) have been prepared via 1,4-addition reaction of hydrazine on chalcones, followed by cyclization of the adduct in the presence of acetic acid. The structural interpretation ofsynthesized compounds was accomplished using various characterization techniques like FT-IR, Ultraviolet/visible spectroscopy,1H NMR and 13C NMR. The synthesized compounds were evaluated for antioxidant, Urease inhibitory and Lipoxygenase inhibitory activities and results revealed that compound 2 showed promising antioxidant, Urease inhibitory and Lipoxygenase inhibitory activity with IC50 values 33.2 ± 0.45, 32.7 ± 0.11 and 42.2 ± 0.77, respectively. Moreover, DNA binding interactions of the N-acetyl pyrazoline derivativeshave also been carried out with SS-DNA (Salmon Sperm DNA) using absorption spectroscopy. Furthermore, molecular docking was conducted for a ready comparison with the experimental data and to determine the interactions involved. ADMET profiling of pyrazoline derivatives was also done using Admet SAR. Besides that, quantum chemical calculations using DFT (density functional theory) were carried out to explore optimized geometries, FMOs (Frontier molecular orbitals), NBOs (Nonbonding orbitals) of synthesized compounds and to predict their NLO (Nonlinear optical) properties. The synthesized compounds showed much better NLO behavior than standard Urea along with a strong agreement between computed and empirically recorded spectral data.

Fabrication of metal-organic salts with heterogeneous conformations of a ligand as dual-functional urease and nitrification inhibitors.

Urease inhibitors (UIs) and nitrification inhibitors (NIs) can greatly reduce nitrogen loss in agriculture soil. However, design and synthesis of an efficient and environmentally friendly dual-functional inhibitor is still a great challenge. Herein, four metal-organic salts (MOSs) based on heterogeneous conformations of the ligand N1,N1,N2,N2-tetrakis(2-fluorobenzyl)ethane-1,2-diamine (L), namely, [2HL]2+·[MCl4]2- (M = Cu, Zn, Cd, and Co), have been synthesized by the "second sphere" coordination method and structurally characterized in detail. Single crystal X-ray diffraction (SCXRD) analyses reveal that the four MOSs are 0D supramolecular structures containing [2HL]2+ and [MCl4]2-, which are connected through non-covalent bonds. Furthermore, the urease and nitrification inhibitory activities of MOSs are evaluated, showing excellent nitrification inhibitory activity with the nitrification inhibitory rate as high as 70.57% on the 28th day in soil cultivation experiment. In particular, MOS 1 shows significant urease inhibitory activity with half maximal inhibitory concentration (IC50) values of 0.89 ± 0.01 μM (0.5 h) and 1.87 ± 0.01 μM (3 h), which can serve as a dual-functional inhibitor.

SYNTHESIS, CRYSTAL STRUCTURES AND UREASE INHIBITION OF ZINC(II) AND COPPER(II) COMPLEXES DERIVED FROM 2-AMINO-N’-(1-(PYRIDIN-2-YL)ETHYLIDENE)BENZOHYDRAZIDE

Two mononuclear zinc(II) and copper(II) complexes, [ZnBr(HL)(NCS)] (1) and [CuL2] (2), where HL and L are the ketone and enolate forms of 2-amino-N’-(1-(pyridin-2-yl)ethylidene)benzohydrazide (HL), have been prepared and characterized by elemental analyses, IR and UV-Vis spectroscopy, as well as single crystal X-ray diffraction studies. The Zn atom in complex 1 is in distorted square pyramidal coordination, with the pyridine N, imino N and carbonyl O atoms of the hydrazone ligand HL and the N atom of the thiocyanate ligand in the basal plane, and with the Br atom at the apical position. The Cu atom in complex 2 is in distorted octahedral coordination, with the pyridine N, imino N and enolate O atoms of one hydrazone ligand L, and the imino N atom of the other hydrazone ligand L in the equatorial plane, and with the pyridine N and enolate O atoms of the other hydrazone ligand L at the axial positions. The hydrazone and the complexes have been assayed for their Jack bean urease activity. As a result, the copper complex has effective urease inhibitory activity with IC50 = 11.9 ± 1.3 μmol L–1. Molecular docking study was performed to investigate the interaction between the complex molecule and the enzyme.

EXTRATOS PIROLENHOSOS DE CASCA DE COCO, ACÁCIA NEGRA E EUCALIPTO: CARACTERIZAÇÃO FÍSICO-QUÍMICA E AVALIAÇÃO IN VITRO COMO POTENCIAIS INIBIDORES DA UREASE

PYROLIGNEOUS ACIDS OF COCONUT SHELL, BLACK WATTLE AND EUCALYPTUS: PHYSICAL-CHEMICAL CHARACTERIZATION AND IN VITRO EVALUATION AS POTENTIAL UREASE INHIBITORS. The increase in food production to meet the demand of the world’s growing population is largely conditioned by the efficiency of agricultural fertilizers. The development of relatively low-cost urease inhibitors and more environmentally friendly ones is a challenge for agriculture, especially because urea is the most used nitrogen fertilizer globally. The pyroligneous acid (PA), a by-product of wood charcoal production, stimulates plant growth, increases crop productivity, improves microbial metabolism, and induces plant tolerance to (a)biotic stresses. This work investigated the in vitro urease inhibitory potential of tree PAs of distinct plant biomass origin and production process. Coconut (Cocus nucifera) shell PA showed the highest urease inhibitory activity, followed by black wattle (Acacia mearnsii) PA and eucalyptus (Eucalyptus urograndis, a hybrid of Eucalyptus grandis and Eucalyptus urophylla). The same sequence was observed for the content of phenols and humic substances (humic acids + fulvic acids). This fact probably justifies the greater inhibitory activity, since both humic substances and some phenols normally present in PA, such as hydroquinone, have already been reported in the literature as urease inhibitors. The results are promising in terms of urease inhibition by PA samples, especially due to its low cost, biodegradability, non-toxicity, high solubility in water, and beneficial effects on plant development.

Enzyme Inhibitory Activities of Extracts and Carpachromene from the Stem of Ficus benghalensis.

Ficus benghalensis is one of the potential medicinal plants which is used locally for the treatment of various ailments such as diabetes, antiasthmatic, and wound healing. To provide a scientific background to these folklores, the current study was designed to evaluate the extract and isolated compound against various enzymes such as ureases, tyrosinase, and phosphodiesterase. The methanolic extract and carpachromene demonstrated a significant urease inhibition effect with maximum percent inhibition of 72.09 and 92.87%, respectively. Regarding the tyrosinase inhibition, the percent antagonist effect of carpachromene and the methanolic extract was 84.80 and 70.98%, respectively. The phosphodiesterase was also significantly antagonized by crude extract and carpachromene with a maximum percent inhibition of 82.98% and 89.54%, respectively. The docking study demonstrated that the carpachromene fits well into the active site of all three enzymes with significant interactions. Carpachromene might possess the potential to inhibit all three enzymes and can effectively treat different diseases associated with the hyperactivity of these enzymes. In conclusion, the crude extract and carpachromene exhibit significant urease, tyrosinase, and phosphodiesterase inhibitory activity which might be used against various diseases. In conclusion, the crude extract and carpachromene exhibit significant urease, tyrosinase, and phosphodiesterase inhibitory activity which might be used against diabetes and bronchoconstriction. Further, the current study provides scientific backup to the folklore (antidiabetic and antiasthmatic) of Ficus benghalensis.

Piperazine-based Semicarbazone Derivatives as Potent Urease Inhibitors: Design, Synthesis, and Bioactivity Screening

Background: An enzyme called urease assists highly pathogenic bacteria in colonizing and maintaining themselves. Accordingly, inhibiting urease enzymes has been shown to be a promising strategy for preventing ureolytic bacterial infections. Objective: This study aimed to synthesize and evaluate the bioactivity of a series of semicarbazone derivatives. Methods: A series of piperazine-based semicarbazone derivatives 5a-o were synthesized and isolated, and their structures were elucidated by 1H-NMR and 13C-NMR spectroscopic techniques besides MS and elemental analysis. The urease inhibition activity of these compounds was evaluated using the standard urease enzyme inhibition kit. An MTT assay was performed on two different cell lines (NIH-3T3 and MCF-7) to investigate the cytotoxicity profile. Results: All semicarbazone 5a-o exhibited higher urease inhibition activity (3.95–6.62 μM) than the reference standards thiourea and hydroxyurea (IC50: 22 and 100 μM, respectively). Derivatives 5m and 5o exhibited the best activity with the IC50 values of 3.95 and 4.05 μM, respectively. Investigating the cytotoxicity profile of the target compound showed that all compounds 5a-o have IC50 values higher than 50 μM for both tested cell lines. Conclusion: The results showed that semicarbazone derivatives could be highly effective as urease inhibitors.

Veronica rosea biomolecule profiling, antioxidant potential, dermoprotective effect, anti-inflammatory and hemostatic activities and enzyme inhibitory action

• Eight flavonoids were isolated from the ethyl acetate extract. two detected for the first time in the genus veronica • Antioxidant evaluation was evaluated using DPPH, FRAP, and total antioxidant capacity. • Sun protection factor was calculated to estimate the dermoprotective activity • In vitro hemostatic activity was measured of plasma re-calcification time (PRT) • Veronica rosea is able to inhibit heat- and hypotonicity-induced hemolysis, • Veronica rosea present acetyl-butyrylcholinesterases and urease effects. : Veronica rosea (Plantaginacea) has been previously studied from a phytochemical perspective. The present research intends to perform an in-depth investigation to identify more secondary metabolites in this plant and to explore its pharmacological potential. : The ethyl acetate extract (EAE) of V. rosea was analysed with different chromatographic methods. The obtained pure products were analysed using nuclear magnetic resonance (NMR) and mass spectrometry to identify the structures of the bioactive compounds. The therapeutic potential of EAE was investigated by performing several in vitro assays. : An advanced spectral analysis enabled the structures of 8 flavonoids to be elucidated. Considerable amounts of phenolic, flavonoid, tannin and anthocyanin compounds were detected in the following quantities: 161.32±4.29 mg gallic acid equivalents (GAE)/g, 179.48±9.86 mg quercetin equivalents (QE)/g dry extract, 36.44±3.37 mg tannic acid equivalents (TAE)/g dry extract and 7.47±0.45 mg cyanidin 3-glucoside (Cy-3-glu) equivalents/100 g of dry weight (DW), respectively. Strong evidence of the antioxidant activity of the EAE was established with diphenyl-1-picrylhydrazyl (DPPH; 50% inhibitory concentration (IC 50 ) = 16.09±0.2 μg/mL), ferric reducing antioxidant power (FRAP; IC 50 = 6.35±0.019 μg/mL) and total antioxidant capacity (161.41±10.76 mg EAA/mg extract). This antioxidant activity leads to important solar protection (solar protection factor (SPF) of 41.53±0.019 at a dose of 0.2 mg/ml). The EAE exerted a moderate to robust effect on stabilizing the red blood cell membrane compared to diclofenac, as well as haemostatic action, for which plasma recalcification times were significantly shortened. The extract inhibited acetylcholinesterase and butyrylcholinesterase activities with IC 50 = 121.6±03.29 µg/mL and 108.94±4.24 µg/mL, respectively, and significantly inhibited urease activity with an IC 50 = 132.77±4.73 μg/mL. : The present findings indicate that V. rosea might be viewed as a potential source of bioactive molecules to improve the prognosis of certain diseases.

Synthetic Transformation of 2-{2-Fluoro[1,1'-biphenyl]-4-yl} Propanoic Acid into Hydrazide-Hydrazone Derivatives: In Vitro Urease Inhibition and In Silico Study.

In the present study, 28 acyl hydrazones (4-31) of flurbiprofen were synthesized in good to excellent yield by reacting different aromatic aldehydes with the commercially available drug flurbiprofen. The compounds were deduced with the help of different spectroscopic techniques like 1H-NMR and HREI-MS and finally evaluated for in vitro urease inhibitory activity. All of the synthesized products demonstrated good inhibitory activities in the range of IC50 = 18.92 ± 0.61 to 90.75 ± 7.71 μM as compared to standard thiourea (IC50 = 21.14 ± 0.42 μM). Compound 30 was found to be the most active among the series better than the standard thiourea. A structure-activity relationship (SAR) study revealed that the presence of electron-donating groups on the phenyl ring plays a prominent role in the inhibition of the urease enzyme. Moreover, in silico molecular modeling analysis was carried out to study the effect of substituents in synthesized derivatives on the binding interactions with the urease enzyme.

Anti-Helicobacter pylori activity of potential probiotic Lactiplantibacillus pentosus SLC13

BackgroundHere, we aimed to evaluate and compare the anti-Helicobacter pylori activity of potential probiotic Lactiplantibacillus pentosus SLC13 to Lactobacillus gasseri BCRC 14619 T and Lacticaseibacillus rhamnosus LGG. Phenotypic assays including growth curve, cell adhesion, and cellular cytotoxicity were performed to characterize SLC13. Anti-H. pylori activity of lactobacilli was determined by the disk diffusion method and co-culture assay. Exopolysaccharide (EPS) was extracted from lactobacilli to test its immune modulation activity, and IL-8 expression in AGS and GES-1 was determined by RT-qPCR.ResultsAll three lactobacilli strains were tolerant to the simulated gastrointestinal conditions. SLC13 showed the highest adhesion ability to AGS and GES-1 cells, compared to LGG and BCRC 14619 T. The coculture assays of SLC13, LGG, and BCRC 14619 T with cells for 4 h showed no significant cytotoxic effects on cells. All tested strains exhibited an inhibitory effect against H. pylori J99. The cell-free supernatant (CFS) of three strains showed activity to inhibit H. pylori urease activity in a dose-dependent manner and the CFS of SLC13 had the highest urease inhibitory activity, compared to LGG and BCRC 14619 T. Only the treatment of AGS cells with SLC13 EPS significantly decreased the IL-8 expression induced by H. pylori infection as compared to cells treated with LGG and BCRC 14619 T EPS.ConclusionsSLC13 possesses potent antimicrobial activity against H. pylori growth, infection, and H. pylori-induced inflammation. These results suggest that SLC13 and its derivatives have the potential as alternative agents against H. pylori infection and alleviate inflammatory response.

1,3,4-Thiadiazole and 1,2,4-triazole-5-thione derivatives bearing 2-pentyl-5-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-one ring: Synthesis, molecular docking, urease inhibition, and crystal structure.

Two series of 1,3,4-thiadiazole (40a-o) and 1,2,4-triazole-5-thione (41a-l) derivatives bearing a 2-pentyl-5-phenyl-1,2,4-triazole-3-one ring were synthesized and then studied for their urease inhibitory activities using thiourea as a standard drug. Among the two groups, the first group (40a-o) did not show good activity while the second group (41a-l) showed excellent activity. Compound 41j (1091.24 ± 14.02 µM) of the second series of compounds showed lower activity than thiourea, while the remaining 11 compounds (41a-i, k, and l) showed better activity than thiourea (183.92 ± 13.14 µM). Among the 11 compounds, 41b (15.96 ± 2.28 µM) having the 3-F group on the phenyl ring showed the highest inhibitory activity. Urease kinetic studies of 41b, which is the most active compound, determined it to have an un-competitive inhibition potential. Moreover, in silico analysis against urease from jack bean with 27 new heterocyclic compounds and the reference molecule was carried out to see the necessary interactions responsible for urease activity. The docking calculations of all compounds supported stronger binding to the receptor than the reference molecule, with high inhibition constants. In addition, compound 40m was characterized by single-crystal X-ray diffraction analysis. X-ray analysis reveals that the structures of the compound 40m crystallize in the monoclinic P21/c space group with the cell parameters: a = 10.2155(9) Å, b = 22.1709(18) Å, c = 21.4858(17) Å, β = 99.677(8)°, V = 4797.0(7) Å3 . X-ray diffraction analyses were also performed to gain insights into the role of weak intermolecular interactions and C-H…X (halogen) interactions in compound 40m that influence the crystal packing.

Synthesis, Characterization, Optical Properties, Molecular Modeling and Urease Inhibition Analysis of Organic Ligands and Their Metal Complexes.

Recently, screening of efficient urease inhibitors by employing organic small molecules metalloderivatives interests the scientific community due to their efficacy for treatment of urease triggered health complications. This study comprises the synthesis, urease inhibition activity, optical analysis and molecular modeling of hydrazinecarbothioamide and hydrazinecarboxamide metalloderivatives. Characterization of synthesized materials was done by UV-visible, fluorescence, NMR and FTIR spectroscopic analysis. Metalloderivatization of ligands induce increment in urease inhibition potential and effect was prominent for copper complexes with 10-fold enhancement, cobalt complex with 3.5 fold's enhancement and palladium with 2-fold increment in the inhibition efficacy toward urease when it was compared with reference urease inhibitor. Zinc and iron complexes cause declined urease inhibition activity of the bare ligand. The overall activity of hydrazinecarbothioamide slightly exceeds than that of hydrazinecarboxamide, possibly due to larger complexation ability of sulfur-based ligand in comparison to oxygenated derivatives i.e., hydrazinecarboxamide. The enzyme inhibition kinetics for the most active complexes represent the mixed type urease inhibition for 3a and competitive urease inhibition for 5a, as determined by Lineweaver-Burk plots. The docked scoring values for both the ligands were calculated to be 61.34, 64.72, 56.68, 62.94, 64.98 and 58.98. Three active hydrogen bonds were observed in docking complex upon computational analysis of most potent metallodrug 3a inside active region of targeted protein.