Synthesis, spectroscopic characterization and antimicrobial activities of benzoxazolone derivatives.

: Background: Pathogenic microbial diseases are now the key virulence in our daily life. Significant research has been carried out in order to trigger the bacterial infections. Amongst the organic molecules, oxazolone and derivatives were found to have excellent bioactivities including antimicrobial activities. METHODS: By keeping in mind the considerable antimicrobial activities of class benzoxazolones, a series of benzoxazolone derivatives 3-16 have been synthesized. Out of which five compounds 10, 11, 14, 15, and 16 were new synthetic derivatives whereas compounds 9, 12, and 13 were already known compounds. These compounds have been synthesized by refluxing of amino phenol and 1,1-carbonyldiimidazole1 (C3H3N2)2CO) (CDI) in a dry THF and then treated with commercially available acid chloride. The structures of the compounds were elucidated on the basis of 1H-NMR, EIMS and elemental analysis. All the compounds were screened for their antibacterial activities and tested by agar well diffusion method. RESULTS: Compounds 14 and 16 showed good activity against S. aureus. Compound 5 showed good while 14 and 16 were found to be most active against E. coli using cefuroxime as a standard. Antifungal activities were carried out by using standard drug nystatin and compounds 4, 5, 9, 11 and compound 12 were found to be active against C. albicans. Compounds 4, 5, 9 and compound 10 showed good while 7, 11, and compound 13 showed excellent activities against Chrysosporium sp. Compounds 6, 7 and compound 12 were found to be most active against A niger and A. flavus, respectively. CONCLUSION: A number of derivatives were identified to have potent antimicrobial activities and may serve as lead compounds for future research.

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.

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).

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 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.

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.

An expeditious synthetic approach towards the synthesis of Bis-Schiff bases (aldazines) using ultrasound.

Aldazines (Bis-Schiff bases) 1-24 were synthesized using aromatic aldehydes (heterocyclic and benzaldehydes) and hydrazine hydrate under reflux using conventional heating and/or via ultrasound irradiation using BiCl3 as catalyst. Ultrasonication conditions with cat. BiCl3 proved to be an effective, environmentally friendly synthetic procedure. This methodology is robust in the presence of electron donating and electron withdrawing groups affording desired products with high yields (>95%) in just a couple of minutes vs. hours using conventional heating.

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.

Benzimidazole, coumrindione and flavone derivatives as alternate UV laser desorption ionization (LDI) matrices for peptides analysis.

BACKGROUND: Matrix-assisted laser desorption/ionization (MALDI) is a soft ionization mass spectrometric technique, allowing the analysis of bio-molecules and other macromolecules. The matrix molecules require certain characteristic features to serve in the laser desorption/ionization mechanism. Therefore, only a limited number of compounds have been identified as ultraviolet- laser desorption/ionization (UV-LDI) matrices. However, many of these routine matrices generate background signals that useful information is often lost in them. We have reported flavones, coumarindione and benzimidazole derivatives as alternate UV-LDI matrices. RESULTS: Thirty one compounds have been successfully employed by us as matrices for the analysis of low molecular weight (LMW) peptides (up to 2000 Da). Two peptides, bradykinin and renin substrate tetra-decapeptide were analyzed by using the newly developed matrices. The MS measurements were made after mixing the matrix solution with analyte by using dried droplet sample preparation procedures. The synthesized matrix materials showed better S/N ratios and minimal background signals for low mass range. Furthermore, pico molar concentrations of [Glu1]-fibrinopeptide B human could be easily analyzed with these matrices. Finally, BSA-digest was analyzed and identified through database search against Swiss-Prot by using Mascot. CONCLUSIONS: These results validate the good performance of the synthesized UV-laser desorption/ionization (LDI) matrices for the analysis of low molecular weight peptides.

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.

Synthesis of benzophenonehydrazone Schiff bases and their in vitro antiglycating activities.

Benzophenonehydrazone Schiff bases 1-25 were synthesized and their in vitro antiglycation potential has been studied. Out of twenty-five compounds, thirteen showed varying degrees of antiglycation activity with IC50 values ranging between 25.7 - 305 µM, if compared with the standard rutin (IC50 = 70.5 ± 0.50 µM). Compounds 21 (2,3- dihydroxybenzaldehyde N-(diphenylmethylene)hydrazine) IC50 = 25.7 ± 0.003 µM, 14 (diphenylmethanone N-[1-(2,4- dihydroxy-5-nitrophenyl)ethylidene]hydrazine) IC50 = 36.6 ± 0.004 µM, 6 (3,4-dihydroxybenzaldehyde N- (diphenylmethylene)hydrazine) IC50 = 49.5 ± 0.001 µM, 13 (diphenylmethanone N-[1-(2,5-dihydroxyphenyl)ethylidene] hydrazine) IC50 = 52.6 ± 0.023 µM, and 15 (diphenylmethanone N-[1-(3,4-dihydroxyphenyl)ethylidene]hydrazine) IC50 = 57 ± 0.002 µM, showed showed much better antiglycation potential superior to the standard rutin. The compounds 7 (2,5- dihydroxybenzaldehyde N-(diphenylmethylene)hydrazine) IC50 = 66 ± 0.002 µM, and 25 (diphenylmethanone N-[1-(2,5- dihydroxyphenyl)propylidene] hydrazine) IC50 = 67.9 ± 0.001 µM showed compareably good antiglycation activity to standard rutin. All compounds were characterized by spectroscopic techniques and gave satisfactory elemental analysis.

Oxindole derivatives: synthesis and antiglycation activity.

Oxindole derivatives 3-25 have been synthesized from commercially available oxindole by refluxing with different aromatic aldehydes in good yields. Their in vitro antiglycation potential has been evaluated. They showed a varying degree of antiglycation activity with IC50 values ranging between 150.4 - 856.7 µM. 3-[(3-Chlorophenyl)methylidene]- 1,3-dihydro-2H-indol-2-one (IC50 = 150.4 ± 2.5 µM) is the most active compound among the series, better than the standard rutin with an IC50 value 294.5 ± 1.50 µM. The structures of the compounds were elucidated by 1H-NMR and mass spectroscopy and elemental analysis. A limited structure-activity relationship has been developed.

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].

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.

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.

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.

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.

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].

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.