Exploring the Synthetic Chemistry of Phenyl-3-(5-aryl-2-furyl)- 2-propen-1-ones as Urease Inhibitors: Mechanistic Approach through Urease Inhibition, Molecular Docking and Structure-Activity Relationship.

Furan chalcone scaffolds belong to the most privileged and promising oxygen-containing heterocyclic class of compounds, which have a wide spectrum of therapeutic applications in the field of pharmaceutics, pharmacology, and medicinal chemistry. This research described the synthesis of a series of twelve novel and seven reported furan chalcone (conventional synthetic approach) analogues 4a-s through the application of microwave-assisted synthetic methodology and evaluated for therapeutic inhibition potential against bacterial urease enzyme. In the first step, a series of nineteen substituted 5-aryl-2-furan-2-carbaldehyde derivatives 3a-s were achieved in moderate to good yields (40-70%). These substituted 5-aryl-2-furan-2-carbaldehyde derivatives 3a-s were condensed with acetophenone via Claisen-Schmidt condensation to furnish 19 substituted furan chalcone scaffolds 4a-s in excellent yields (85-92%) in microwave-assisted synthetic approach, while in conventional methodology, these furan chalcone 4a-s were furnished in good yield (65-90%). Furan chalcone structural motifs 4a-s were characterized through elemental analysis and spectroscopic techniques. These nineteen (19)-afforded furan chalcones 4a-s were screened for urease inhibitory chemotherapeutic efficacy and most of the furan chalcones displayed promising urease inhibition activity. The most active urease inhibitors were 1-phenyl-3-[5-(2',5'-dichlorophenyl)-2-furyl]-2-propen-1-one 4h with an IC50 value of 16.13 ± 2.45 µM, and 1-phenyl- 3-[5-(2'-chlorophenyl)-2-furyl] -2-propen-1-one 4s with an IC50 value of 18.75 ± 0.85 µM in comparison with reference drug thiourea (IC50 = 21.25 ± 0.15 µM). These furan chalcone derivatives 4h and 4s are more efficient urease inhibitors than reference drug thiourea. Structure-activity relationship (SAR) revealed that the 2,5-dichloro 4h and 2-chloro 4s moiety containing furan chalcone derivatives may be considered as potential lead reagents for urease inhibition. The in silico molecular docking study results are in agreement with the experimental biological findings. The results of this study may be helpful in the future drug discovery and designing of novel efficient urease inhibitory agents from this biologically active class of furan chalcones.

Synthesis and in vitro cholinesterase inhibitory potential of dihydropyridine derivatives.

Twelve derivatives of dihydropyridine derivatives (6-17) were synthesized and evaluated for in-vitro cholinesterases (AChE, BChE) inhibitory activity. All compounds showed potent activity with IC50 values between 0.21±0.003 to 147.14±0.12µM for AChE and among them five compounds showed potent activity with IC50 values 17.16±0.02 to 231.6±0.12µM for BChE when compared with standard Eserine (IC50 = 0.85±0.0001 µM (AChE) & 0.04±0.0001µM (BChE). The most potent compound 11 can be considered as potential lead compound showed an inhibition of 95.35±0.11 and IC50= 0.21±0.003 while compound 7 showed an inhibition of 83.45±0.13 and IC50= 17.16±0.02. It is concluded from structural activity relationship that the presence of nitro group at C-2 and C-4 position of dihydropyridine ring increase the acetyl cholinesterase and butyrylcholinesterase activities of these compounds while presence of -Br and -Cl also enhances the activities.

Biologically active scaffolds: Synthesis, characterization and studies of oxino bis-pyrazoles by environmental friendly method.

In the present communication, synthesis of bis-pyrazolones containing aryl motifs (4-14) and their α-glucosidase inhibitory activity, hemolytic and antihemolytic activities were reported. The newly synthesized compounds were characterized by analytical techniques such 1H-NMR, 13C-NMR, IR, mass spectrometry and compound No 4 additionally by X-ray crystallography. Compounds 4, 12, 14 were obtained in more than 85% yield. In comparison to typical acarbose (IC50 = 37.38±0.12µM), all synthesized compounds showed potent activity with IC50 values between 31.26±0.11 to 396.25±0.18µM. The most potent compounds 6, 8 and 11 showed IC50 values within the range of 31.26±0.11 to 37.48±0.12µM. Compounds 7, 10, 12 and 13 showed IC50 values within the range of 65.23±0.12 to 154.87±0.16µM, while compounds 4, 5 and 9 showed moderate inhibition with IC50 values 286.56±0.16 to 396.25±0.18µM. Structure-activity relationship (SAR) studies, suggests that electron withdrawing groups played a crucial role in enhancing α-glucosidase inhibitory effects of title compounds. In addition, results of the hemolytic and antihemolytic activity studies indicated that compound 13 possessed moderate levels of hemolytic and highest anti- hemolytic activity while 8 showed low anti- hemolytic and high hemolytic activity.

Imidazole-pyrazole hybrids: Synthesis, characterization and in-vitro bioevaluation against α-glucosidase enzyme with molecular docking studies.

Herein, substituted imidazole-pyrazole hybrids (2a-2n) were prepared via a multi component reaction employing pyrazole-4-carbaldehydes (1a-1d), ammonium acetate, benzil and arylamines as reactants. All the new compounds were characterized through their spectral and elemental analyses. Further these compounds were tested against α-glucosidase enzyme. The compounds 2k, 2l and 2n possessed good inhibition potencies, however, compounds 2f (IC50 value: 25.19 ±â€¯0.004 µM) and 2m (IC50 value: 33.62 ±â€¯0.03 µM) were the most effective compounds of the series. Furthermore, molecular docking helped to understand the binding interactions of 2f and 2m with the understudy yeast's α-glucosidase enzyme.

Biological evaluation of new imidazole derivatives tethered with indole moiety as potent α-glucosidase inhibitors.

A series of triarylimidazoles substituted with 2-arylindoles (4a-4j) were prepared and evaluated for their in vitro α-Glucosidase inhibition. α-Glucosidase inhibition assay displayed a new class of highly potent agents The new compounds showed significant α-glucosidase inhibitory activity as compared to the standard inhibitor acrabose. Structures of synthesized compounds were determined by using Mass spectrometry FT-IR, 1H NMR and 13C NMR.

Hetarylcoumarins: Synthesis and biological evaluation as potent α-glucosidase inhibitors.

In search of better α-glucosidase inhibitors, a series of novel hetarylcoumarins (3a-3j) were designed and synthesized through a facile multicomponent route where p-toluenesulfonic acid (PTSA) was explored as an efficient catalyst. These new scaffolds were further evaluated for their α-glucosidase inhibition potentials. All the derivatives exhibited good to excellent results which were comparable or even better than of standard drug acarbose. Of these compounds, a dihalogenated compound 3f was found to be the most effective one with IC50: 2.53±0.002µM. Molecular docking has predicted the plausible binding interactions of compounds 3f, 3g and 3j with α-glucosidase.

Green synthesis, inhibition studies of yeast α-glucosidase and molecular docking of pyrazolylpyridazine amines.

An efficient and environmentally benign simple fusion reaction of 3-chloro-6-(3,5-dimethyl-1H-pyrazol-1-yl)pyridazine (1a) or 3-chloro-6-(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)pyridazine (2a) with different aliphatic/aromatic amines have produced a series of novel pyrazolylpyridazine amines (4a-4c &5a-5m). All compounds exhibited moderate in vitro yeast α-glucosidase inhibition except m-chloro derivative 5g, which was found potent inhibitor of this enzyme with IC50 value of 19.27±0.005µM. The molecular docking further helped in understanding the structure activity relationship of these compounds including 5g.

In search of new α-glucosidase inhibitors: Imidazolylpyrazole derivatives.

Under three different reaction conditions (conventional heating, microwave irradiations and amino acid catalysis), a series of imidazolylpyrazoles (2a-2k) were synthesized in good to excellent yields from a mixture of three precursors: aryl(hetaryl)pyrazole-4-carbaldehydes (1a-1k), benzil and ammonium acetate. α-Glucosidase inhibition assay revealed a new class of highly potent agents wherein each compound displayed significant inhibitory potentials (in terms of percentage inhibition and relative IC50 values) as compared to that of the reference drug (Acarbose). Moreover, molecular modelling of most potent compounds 2h, 2j and 2k also helped in understanding the structure and activity relationship.

Discovery of indole-based tetraarylimidazoles as potent inhibitors of urease with low antilipoxygenase activity.

A series of tetraarylimidazoles (5A-5O) were prepared by one pot four component condensation reactions of 2-arylindole-3-carbaldehydes, substituted anilines, benzil and ammonium acetate in acetic acid. The synthesized compounds exhibited potent antiurease activity with IC50 values ranging from 0.12 ± 0.06 µM to 29.12 ± 0.18 µM as compared with thiourea. However, low inhibition profiles were observed for lipoxygenase. The data show that tetraarylimidazoles containing a substituted 2-penylindole have emerged as a new class of potent inhibitors of urease enzyme.

Synthesis of novel indenoquinoxaline derivatives as potent α-glucosidase inhibitors.

A series of new N-(11H-Indeno[1,2-b]quinoxalin-11-ylidene)benzohydrazide derivatives (3a-3p) were synthesized and evaluated for their α-glucosidase inhibitory activity. The synthesized compounds 3d, 3f, 3g, 3k, 3n, 3p and 4 showed significant α-glucosidase inhibitory activity as compared to acrabose, a standard drug used to treat type II diabetes. Structures of the synthesized compounds were determined by using FT-IR, (1)H NMR, (13)C NMR, mass spectrometry and elemental analysis techniques.

Biosorption of Pb(II) and Cr(III) from aqueous solutions: breakthrough curves and modeling studies.

The sorption capacity parameters obtained for batch studies provide useful information about biosorption system. However, such data fail to explain the process under continuous-flow conditions. The present study is an attempt to explore the biosorption of Pb(II) and Cr(III) by straw from local wheat (Triticum aestivum). The biosorbent has been characterized by using Fourier transform infrared spectroscopy and surface area and elemental analyses and found to be porous and polyfunctional. S-shaped breakthrough curves were obtained at different column heights for the both metal ions. Various breakthrough parameters and saturation times have been determined. The column data have been successfully used to study the Bohart-Adams' bed depth service time (BDST) model and Yoon and Nelson's model. It was found that BDST model quite efficiently explained the whole column data whereas Yoon and Nelson model could explain it below 90% breakthrough concentration. The predicted and calculated BDST parameters were in agreement with each other. Yoon and Nelson's constant decreased with an increase in the column height for both metal ions. Effect of change in flow rate on the Pb(II) biosorption has also been discussed with respect to BDST approach.

Ethyl 2-(pyridine-4-carboxamido)-4,5,6,7-tetra-hydro-1-benzothio-phene-3-carboxyl-ate.

In the title compound, C(17)H(18)N(2)O(3)S, the dihedral angles between the thio-phene ring and the ethyl ester group and the pyridine-4-carboxamide unit are 7.1 (2) and 9.47 (11)°, respectively. An intra-molecular N-H⋯O hydrogen bond generates an S(6) ring. In the crystal, inversion dimers linked by pairs of C-H⋯O hydrogen bonds between the tetra-hydro-1-benzothio-phene and the pyridine-4-carboxamide residues generate R(2) (2)(16) loops. There exists positional disorder in three methelene groups of the cyclo-hexane ring and the terminal C atom of the ethyl ester side chain in a 0.691 (14):0.309 (14) occupancy ratio.

Ethyl 2-acet-amido-4,5,6,7-tetra-hydro-1-benzothio-phene-3-carboxyl-ate.

In the title compound, C(13)H(17)NO(3)S, the dihedral angles between the thio-phene ring and the ethyl ester and acetamide groups are 5.21 (13) and 10.06 (16)°, respectively. The cyclo-hezene ring adopts a half-chair conformation. An S(6) ring is formed due to an intra-molecular N-H⋯O hydrogen bond. In the crystal, mol-ecules are linked by C-H⋯O inter-actions between the tetra-hydro-1-benzothio-phene unit and the ethyl ester group, forming C(7) chains propagating along the b-axis direction.

(4Z)-4-[(2E)-1-Hy-droxy-3-(3-nitro-phen-yl)prop-2-en-1-yl-idene]-3-methyl-1-(4-methyl-phen-yl)-1H-pyrazol-5(4H)-one.

In the title compound, C(20)H(17)N(3)O(4), the dihedral angles between the heterocyclic ring and the toluene and nitro-benzene rings are 4.21 (15) and 11.43 (14)°, respectively. The whole mol-ecule is close to planar (r.m.s. deviation for the 27 non-H atoms = 0.171 Å). Two S(6) rings are formed due to intra-molecular C-H⋯O and O-H⋯O hydrogen bonds. In the crystal, inversion dimers linked by pairs of C-H⋯O bonds generate R(2) (2)(10) loops and further C-H⋯O bonds link the dimers along the b-axis direction. There exist π-π inter-actions between the heterocyclic rings at a centroid-centroid distance of 3.7126 (10) Šand between the centroids of the benzene rings at a distance of 3.8710 (16) Å.

6-Chloro-N-(2-meth-oxy-phen-yl)pyridazin-3-amine.

The asymmetric unit of the title compound, C(11)H(10)ClN(3)O, contains two geometrically different mol-ecules, A and B, in both of which the pyridazine rings are essentially planar with r.m.s. deviations of 0.0137 and 0.0056Å, respectively. In mol-ecule A, the dihedral angle between the pyridazine and benzene rings is 6.5 (2)°, whereas in mol-ecule B it is 27.93 (7)°. In mol-ecule B, an intramolecular N-H⋯O hydrogen bond forms an S(5) ring motif. In both molecules, S(6) ring motifs are present due to non-classical C-H⋯N hydrogen bonds. The π-π inter-actions between the pyridazine rings of A mol-ecules [3.4740 (13) Å] and B mol-ecules [3.4786 (17) Å] have very similar centroid-centroid separations. π-π Inter-actions also occur between the benzene rings of B mol-ecules with a centroid-centroid separation of 3.676 (2) Šand a slippage of 1.02 Å. In the crystal, the mol-ecules are linked into chains extending along [010] by C-H⋯N and C-H⋯Cl interactions.

Synthesis of novel quinoxalinone derivatives by conventional and microwave methods and assessing their biological activity.

In this study, twenty-one arylaminoquinoxalinone derivatives were synthesized and their antibacterial activities against Staphylococci aureus, Pseudomonas aureus, Escherichia coli, Bacillus subtilis, Salmonella typhi, and Shigella pneumoniae were evaluated relative to known antibiotics; augmentin, ampicillin, and chloramphenicol. The insecticidal activities of the prepared compounds were also investigated against Tribolium castaneum using permethrin as a standard insecticide. The derivatives were synthesized using both conventional and microwave techniques. Their structures were confirmed using spectral techniques and elemental analysis.

3-Chloro-6-[2-(cyclo-pentyl-idene)hydrazin-1-yl]pyridazine.

The asymmetric unit of the title compound, C(9)H(11)ClN(4), contains two virtually planar mol-ecules that differ in conformation about the bond connecting the hydrazine and pyridazine units. The 3-chloro-6-hydrazinylpyridazine and cyclo-pentane groups are oriented at dihedral angles of 4.5 (3) and 8.8 (4)° in the two mol-ecules. In the crystal, the mol-ecules form a one dimensional polymeric structure extending along the a axis via N-H⋯N hydrogen bonds. The crystal stucired was an inversion twin [ratio of the twin domains = 0.73 (9):0.27 (9)].

3,4-Dimethyl-1-phenyl-pyrano[2,3-c]pyrazol-6(1H)-one.

In the title compound, C(14)H(12)N(2)O(2), the dihedral angle between the phenyl ring and the 3,4-dimethyl-pyrano[2,3-c]pyrazol-6(1H)-one system is 7.28 (6)°. An intra-molecular C-H⋯O inter-action generates an S(6) ring. In the crystal, the mol-ecules are linked by C-H⋯O hydrogen bonds, forming C(8) chains. C-H⋯π and π-π inter-actions [centroid-centroid separation = 3.6374 (12) Å] further consolidate the packing.

Diethyl 2-{[(5-oxo-5H-thio-chromeno[2,3-b]pyridin-7-yl)amino]-methyl-idene}propane-dioate.

In the title compound, C(15)H(14)O(2)S, the three fused rings are roughly coplanar, the largest deviation from the mean plane being 0.1285 (13) Šfor the S atom. An intra-molecular N-H⋯O hydrogen bond generates an S6 ring. In the crystal, inter-molecular C-H⋯O hydrogen bonds form R(2) (2)(14), R(2) (2)(13) and R(3) (2)(17) ring motifs, building a layer parallel to (100).

Biosorption of heavy metal ions using wheat based biosorbents--a review of the recent literature.

Conventional technologies for the removal/remediation of toxic metal ions from wastewaters are proving expensive due to non-regenerable materials used and high costs. Biosorption is emerging as a technique offering the use of economical alternate biological materials for the purpose. Functional groups like carboxyl, hydroxyl, sulphydryl and amido present in these biomaterials, make it possible for them to attach metal ions from waters. Every year, large amounts of straw and bran from Triticum aestivum (wheat), a major food crop of the world, are produced as by-products/waste materials. The purpose of this article is to review rather scattered information on the utilization of straw and bran for the removal/minimization of metal ions from waters. High efficiency, high biosorption capacity, cost-effectiveness and renewability are the important parameters making these materials as economical alternatives for metal removal and waste remediation. Applications of available adsorption and kinetic models as well as influences of change in temperature and pH of medium on metal biosorption by wheat straw and wheat bran are reviewed. The biosorption mechanism has been found to be quite complex. It comprises a number of phenomena including adsorption, surface precipitation, ion-exchange and complexation.