The immunomodulation potential of the synthetic derivatives of benzothiazoles: Implications in immune system disorders through in vitro and in silico studies.

Benzothiazole and its natural or synthetic derivatives have been used as precursors for several pharmacological agents for neuroprotective, anti-bacterial, and anti-allergic activities. The objective of the present study was to evaluate effects of benzothiazole analogs (compounds 1-26) for their immunomodulatory activities. Eight compounds (2, 4, 5, 8-10, 12, and 18) showed potent inhibitory activity on PHA-activated peripheral blood mononuclear cells (PBMCs) with IC50 ranging from 3.7 to 11.9 µM compared to that of the standard drug, prednisolone <1.5 µM. Some compounds (2, 4, 8, and 18) were also found to have potent inhibitory activities on the production of IL-2 on PHA/PMA-stimulated PBMCs with IC50 values ranging between <4.0 and 12.8 µM. The binding interaction of these compounds was performed through silico molecular docking. Compounds 2, 8, 9, and 10 significantly suppressed oxidative burst ROS production in phagocytes with IC50 values between <4.0 and 15.2 µM. The lipopolysaccharide (LPS)-induced nitrites in murine macrophages cell line J774 were found to be inhibited by compounds 4, 8, 9, and 18 at a concentration of 25 µg/mL by 56%, 91%, 58%, and 78%, respectively. Furthermore, compounds 5, 8, 12, and 18 showed significant (P<0.05) suppressive activity on Th-2 cytokine, interleukin 4 (IL-4) with an IC50 range of <4.0 to 40.3 µM. Interestingly compound 4 has shown a selective inhibitory activity on IL-2 and T cell proliferation (naïve T cell proliferation stage) rather than on IL-4 cytokine, while compound 12 displayed an interference with T-cell proliferation and IL-4 generation. Moreover compound 8 and 18 exert non-selective inhibition on both IL-2 and IL-4 cytokines, indicating a better interference with stage leading to humoral immune response and hence possible application in autoimmune diseases.

Evaluation of bisindole as potent ß-glucuronidase inhibitors: synthesis and in silico based studies.

Bisindole analogs 1-17 were synthesized and evaluated for their in vitro ß-glucuronidase inhibitory potential. Out of seventeen compounds, the analog 1 (IC50=1.62±0.04 µM), 6 (IC50=1.86±0.05 µM), 10 (IC50=2.80±0.29 µM), 9 (IC50=3.10±0.28 µM), 14 (IC50=4.30±0.08 µM), 2 (IC50=18.40±0.09 µM), 19 (IC50=19.90±1.05 µM), 4 (IC50=20.90±0.62 µM), 7 (IC50=21.50±0.77 µM), and 3 (IC50=22.30±0.02 µM) showed superior ß-glucuronidase inhibitory activity than the standard (d-saccharic acid 1,4-lactone, IC50=48.40±1.25 µM). In addition, molecular docking studies were performed to investigate the binding interactions of bisindole derivatives with the enzyme. This study has identified a new class of potent ß-glucouronidase inhibitors.

Structure-based design, synthesis and biological evaluation of ß-glucuronidase inhibitors.

Using structure-based virtual screening approach, a coumarin derivative (1) was identified as ß-glucuronidase inhibitor. A focused library of coumarin derivatives was synthesized by eco-benign version of chemical reaction, and all synthetic compounds were characterized by using spectroscopy. These compounds were found to be inhibitor of ß-glucuronidase with IC50 values in a micromolar range. All synthetic compounds exhibited interesting inhibitory activity against ß-glucuronidase, however, their potency varied substantially from IC50 = 9.9-352.6 µM. Of twenty-one compounds, four exhibited a better inhibitory profile than the initial hit 1. Interestingly, compounds 1e, 1k, 1n and 1p exhibited more potency than the standard inhibitor with IC50 values 34.2, 21.4, 11.7, and 9.9 µM, respectively. We further studied their dose responses and also checked our results by using detergent Triton ×-100. We found that our results are true and not affected by detergent.

Evaluation of the thiazole Schiff bases as ß-glucuronidase inhibitors and their in silico studies.

Twenty eight (28) derivatives 2-29 were synthesized and four analogs were found to exhibit single-digit IC(50) values as ß-glucuronidase inhibitors. Molecular modeling indicates that three factors: substituent R, lone pair on the nitrogen of azomethine part, and the interactions made by the main skeleton of the molecule, determined the enzyme inhibitory potential of these compounds. The planar conformation of the molecules allows them to fit deep inside the pocket while blocking the entry of other physiological substrates seems to play an important role in their activity.

Phenoxyacetohydrazide Schiff bases: ß-glucuronidase inhibitors.

Phenoxyacetohydrazide Schiff base analogs 1-28 have been synthesized and their in vitro ß-glucouoronidase inhibition potential studied. Compounds 1 (IC50=9.20±0.32 µM), 5 (IC50=9.47±0.16 µM), 7 (IC50=14.7±0.19 µM), 8 (IC50=15.4±1.56 µM), 11 (IC50=19.6±0.62 µM), 12 (IC50=30.7±1.49 µM), 15 (IC50=12.0±0.16 µM), 21 (IC50=13.7±0.40 µM) and 22 (IC50=22.0±0.14 µM) showed promising ß-glucuronidase inhibition activity, better than the standard (D-saccharic acid-1,4-lactone, IC50=48.4±1.25 µM).

Metallic nanoentities: Bio-engineered silver, gold, and silver/gold bimetallic nanoparticles for biomedical applications.

This present study reports the biogenic synthesis of silver nanoparticles (AgNPs), gold nanoparticles (AuNPs) and Ag/Au bimetallic nanoparticles (BNPs) using bark extract of plant Tamarix aphylla (T.A). The bark extract contained total polyphenolic compounds and total flavonoids as 0.0362 mg/mg and 0.2928 mg/mg of the dried bark extract respectively. Silver nitrate (AgNO3) and hydrogen tetra chloroaurate trihydrate (HAuCl4.3H2O) were used as precursors while deionised water and methanol (CH3OH) were used as solvents. Synthesized nanoparticles were characterized through UV-visible spectroscopy, SEM (scanning electron microscopy), TEM (transmission electron microscopy) and FTIR (Fourier transform infrared) for their morphology, structure, and identification of different functional groups. The UV-visible spectra of AgNPs, AuNPs and Ag/Au BNPs showed peaks at 436, 532 and 527 nm respectively due to the excitation of Surface Plasmon Resonance. SEM and TEM images showed spherical and well distributed nanoparticles (NPs) with particle size as 29 nm (AgNPs), 13 nm (AuNPs) and 26 nm (Ag/Au BNPs). The synthesized NPs are significantly active against inhibition of free radicals, α-amylase, α-glucosidase and have anti inflammatory potential with AgNPs having the highest percent activity at 400 µg/ml, followed by Ag/Au BNPs. The same trend (AgNPs > Ag/AuBNPs > AuNPs) has been observed at all concentrations i.e. 100 µg/ml, 200 µg/ml and 400 µg/ml. AuNPs have shown lowest activity at all concentrations. So the current study strongly confirms use of T.A bark extract as reducing agent for synthesis of metal NPs and opens up a new possibility of using these green synthesized NPs as biomedicines. We also suggest further in vivo investigation to report any side effects if present.

5-Chloro-2-(4-meth-oxy-phen-yl)-1,3-benzo-thia-zole.

In the title compound, C14H10ClNOS, the dihedral angle between the benzothia-zole ring system and the meth-oxy-substituted benzene ring is 8.76 (16)°. In the crystal, mol-ecules are stacked in columns along the c axis and no significant inter-molecular inter-actions are observed.

Hypervalent iodine/TEMPO-mediated oxidation in flow systems: a fast and efficient protocol for alcohol oxidation.

Hypervalent iodine(III)/TEMPO-mediated oxidation of various aliphatic, aromatic and allylic alcohols to their corresponding carbonyl compounds was successfully achieved by using microreactor technology. This method can be used as an alternative for the oxidation of various alcohols achieving excellent yields and selectivities in significantly shortened reaction times.

1-(3-Meth-oxy-phen-yl)-2-(phenyl-sulfon-yl)ethan-1-one.

In the title compound, C(15)H(14)O(4)S, the dihedral angle between the benzene and phenyl rings is 88.74 (10)°. In the crystal, mol-ecules are linked into a three-dimensional network by C-H⋯O hydrogen bonds and π-π stacking inter-actions [centroid-centroid distances = 3.6092 (13)-3.8651 (13) Å].

5-Chloro-2-phenyl-1,3-benzothia-zole.

In the structure of the title compound, C(13)H(8)ClNS, the dihedral angle between the benzothia-zole ring system and the phenyl ring is 7.11 (8)°. In the crystal, mol-ecules are arranged parallel to the c axis.

2-(5-Chloro-1,3-benzothia-zol-2-yl)-4-meth-oxy-phenol.

In the mol-ecule of the title compound, C(14)H(10)ClNO(2)S, the dihedral angle between the almost planar benzothia-zole ring system [maximum deviation = 0.005 (2) Å] and the benzene ring is 1.23 (9)°. The conformation of the mol-ecule is stabilized by an intra-molecular O-H⋯N hydrogen bond, forming an S(6) ring motif. In the crystal, mol-ecules are linked into layers parallel to the ac plane by C-H⋯O hydrogen bonds and π-π stacking inter-actions [centroid-centroid distance = 3.7365 (12) Å].

5-Chloro-2-(3,4,5-trimeth-oxy-phen-yl)-1,3-benzothia-zole.

In the title compound, C(16)H(14)ClNO(3)S, the dihedral angle between the almost-planar benzothia-zole ring system [maximum deviation = 0.012 (3) Å] and the aromatic ring of the trimeth-oxy-phenyl group is 15.56 (6)°. In the crystal, the mol-ecules are arranged into layers parallel to the bc plane, held together only by weak van der Waals forces.

3,5a,9-Trimethyl-8-(2-phenylhydrazin-1-ylidene)-4,5,5a,9b-tetrahydro-3aH,8H-naphtho[1,2-b]furan-2(3H)-one.

The title compound, C(21)H(24)N(2)O(2), is a phenyl hydrazine derivative of the well known anthelminthic agent α-santonin, which is composed of three fused rings (benzodieneone, cyclo-hexane and γ-lactone). The cyclo-hexa-dienone ring adopts a boat conformation, the cyclo-hexane ring is in a chair conformation and the trans-fused γ-lactone ring adopts a C-envelope conformation. In the crystal, mol-ecules are linked by N-H⋯O and C-H⋯O hydrogen bonds, forming chains along the a axis.

8-[(2-Hy-droxy-phen-yl)imino]-3,5a,9-trimethyl-3a,4,5,5a,8,9b-hexa-hydro-naphtho-[1,2-b]furan-2(3H)-one.

The title compound, C(21)H(23)NO(3), is a phenyl-imine derivative of the well known anthelmintic agent α-santonin. The trans-fused cyclo-hexane and γ-lactone rings of the α-santonin ring system adopt chair and envelope conformations, respectively, whereas the hexa-diene ring is approximately planar [maximum deviation = 0.029 (4) Å] and forms a dihedral angle of 62.30 (11)° with the benzene ring. An intra-molecular O-H⋯N hydrogen bond is observed.

6-Methyl-4-oxo-4H-chromene-3-carbaldehyde.

In the title compound, C(11)H(8)O(3), the benzopyran-4-one or chromone ring system is almost planar, with a maximum deviation of 0.045 (2) Å. The crystal structure is stablized by π-π inter-actions between the benzene and pyran rings of inversion-related mol-ecules stacked along the b axis, with a centroid-centroid distance of 3.5463 (12) Å

Ethyl (E)-3-(6-methyl-4-oxo-4H-chromen-3-yl)prop-2-enoate.

In the title compound, C(15)H(14)O(4), the chromone ring system is close to being planar [maximum deviation = 0.015 (2) Å]. The double bond of the ethyl prop-2-enoate chain adopts an E conformation and an intra-molecular C-H⋯O hydrogen bond generates an S6 ring. In the crystal, inversion dimers linked by pairs of C-H⋯O hydrogen bonds generate R(2) (2)(14) loops. Weak π-π inter-actions [centroid-centroid distance = 3.8493 (12) Å] also occur.

Synthesis, characterization and biological screening of sulfonamides derived form 2-phenylethylamine.

In the present study, a series of N-substituted derivatives of 2-phenylethylamine has been synthesized. The reaction of 2-phenylethylamine (1) with benzene sulfonyl chloride (2) yielded N-(2-phenylethyl) benzenesulfonamide (3), which further on treatment with alkyl/acyl halides (4a-i) in the presence of sodium hydride furnished into N-substituted sulfonamides (5a-i). These derivatives were characterized by IR, (1)H-NMR and EI-MS and then screened against acetyl cholinesterase (AChE), butyryl cholinesterase (BChE) and lipoxygenase enzyme (LOX) and were found to be potent inhibitors of butyryl cholinesterase only.

3D-QSPR method of computational technique applied on red reactive dyes by using CoMFA strategy.

Cellulose fiber is a tremendous natural resource that has broad application in various productions including the textile industry. The dyes, which are commonly used for cellulose printing, are "reactive dyes" because of their high wet fastness and brilliant colors. The interaction of various dyes with the cellulose fiber depends upon the physiochemical properties that are governed by specific features of the dye molecule. The binding pattern of the reactive dye with cellulose fiber is called the ligand-receptor concept. In the current study, the three dimensional quantitative structure property relationship (3D-QSPR) technique was applied to understand the red reactive dyes interactions with the cellulose by the Comparative Molecular Field Analysis (CoMFA) method. This method was successfully utilized to predict a reliable model. The predicted model gives satisfactory statistical results and in the light of these, it was further analyzed. Additionally, the graphical outcomes (contour maps) help us to understand the modification pattern and to correlate the structural changes with respect to the absorptivity. Furthermore, the final selected model has potential to assist in understanding the characteristics of the external test set. The study could be helpful to design new reactive dyes with better affinity and selectivity for the cellulose fiber.

Synthesis and leishmanicidal activity of 2,3,4-substituted-5-imidazolones.

Twenty-nine imidazolones 1-29 were synthesized and were randomly screened for their in vitro anti-leishmanial potential. Compound 17 showed a good anti-leishmanial activity with an IC50 value of 12.98 +/- 0.32 microg/mL. Compounds 14 and 24 were also found to be moderately active (IC50 values 28.20 +/- 0.03 and 41.12 +/- 0.32 microg/mL, respectively). The activity was compared with that of standard drugs, amphotericin B (IC50 = 0.12 +/- 0.41 microg/mL) and pentamidine (IC50 = 2.56 +/- 0.10 microg/mL).

Schiff bases of 3-formylchromone as thymidine phosphorylase inhibitors.

3-Formylchromone (1), 3-methyl-7-hydroxychromone (2) and Schiff bases of 3-formylchromone 3-19 have been synthesized and their anti-thymidine phosphorylase inhibitory activity was evaluated. Compounds 1-19 showed a varying degree of thymidine phosphorylase inhibition with IC(50) values 19.77+/-3.25 to 480.21+/-2.34 microM. Their activity was compared with the standard 7-deazaxanthine (IC(50)=39.28+/-0.76 microM). Compound 12 showed an excellent thymidine phosphorylase inhibitory activity with an IC(50) value of 19.77+/-3.25 microM, better than the standard. Compound 4 also showed an excellent inhibitory activity (IC(50)=40.29+/-4.56 microM). The parent 3-formylchromone (1) and 3-methyl-7-hydroxychromone (2) were found to be inactive. The structures of the compounds were elucidated by using spectroscopic techniques, including (1)H NMR, EI MS, IR, UV and elemental analysis.