4H-Chromene-based anticancer agents towards multi-drug resistant HL60/MX2 human leukemia: SAR at the 4th and 6th positions.

4H-Chromene-based compounds, for example, CXL017, CXL035, and CXL055, have a unique anticancer potential that they selectively kill multi-drug resistant cancer cells. Reported herein is the extended structure-activity relationship (SAR) study, focusing on the ester functional group at the 4th position and the conformation at the 6th position. Sharp SARs were observed at both positions with respect to cellular cytotoxic potency and selectivity between the parental HL60 and the multi-drug resistant HL60/MX2 cells.

Structure-activity relationship (SAR) study of ethyl 2-amino-6-(3,5-dimethoxyphenyl)-4-(2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (CXL017) and the potential of the lead against multidrug resistance in cancer treatment.

Multidrug resistance (MDR) against standard therapies poses a serious challenge in cancer treatment, and there is a clinical need for new anticancer agents that would selectively target MDR malignancies. Our previous studies have identified a 4H-chromene system, CXL017 (4) as an example, that can preferentially kill MDR cancer cells. To further improve its potency, we have performed detailed structure-activity relationship (SAR) studies at the 3, 4, and 6 positions of the 4H-chromene system.

Experimental and GIAO 15N NMR study of substituent effects in 1H-tetrazoles.

A series of 1-aryl/alkyl-1H-1,2,3,4-tetrazoles, 5-substituted 1H-tetrazoles, and 1,5- and 2,5-disubstituted 1H-tetrazoles were studied by a combination of experimental NMR (natural abundance (15)N, (15)N/(1)H HMBC, and (13)C) and computational GIAO-NMR techniques to explore substituent effects on (15)N (and (13)C) NMR chemical shifts in the tetrazole (TA) moiety. Computed (15)N chemical shifts via GIAO-B3LYP/6-311+G(2d,p) calculations gave satisfactory results in comparison with experimental data. Whereas N-alkylation leads to large (15)N chemical shift changes, changes in the N(1)-aryl derivatives bearing diverse substituent(s) are generally small except for polar ortho-substituents (COOH, NO(2)).

Ethylammonium nitrate (EAN)/Tf2O and EAN/TFAA: ionic liquid based systems for aromatic nitration.

Acting as in situ sources of triflyl nitrate (TfONO(2)) and trifluoroacetyl nitrate (CF(3)COONO(2)), the EAN/Tf(2)O and EAN/TFAA systems, generated via metathesis in the readily available ethylammonium nitrate (EAN) ionic liquid as solvent, are powerful electrophilic nitrating reagents for a wide variety of aromatic and heteroaromatic compounds. Comparative nitration experiments indicate that EAN/Tf(2)O is superior to EAN/TFAA for nitration of strongly deactivated systems. Both systems exhibit low substrate selectivity (K(T)/K(B) = 5-10) in between values reported for covalent nitrates and preformed nitronium salts.

Electrophilic chemistry of propargylic alcohols in imidazolium ionic liquids: propargylation of arenes and synthesis of propargylic ethers catalyzed by metallic triflates [Bi(OTf)3, Sc(OTf)3, Yb(OTf)3], TfOH, or B(C6F5)3.

Metallic triflates M(OTf)(3) (M = Bi, Sc, Yb), immobilized in imidazolium ionic liquids [BMIM][BF(4)], [BMIM][PF(6)] and [BMIM][OTf] are efficient systems for one-pot reactions of propargylic alcohols 1,3-diphenyl-2-propyn-1-ol Ia, 1-methyl-3-phenyl-2-propyn-1-ol Ib, and 2-pentyn-1-ol Ic, with a wide range of arenes bearing activating substituents, under mild conditions. The [BMIM][PF(6)]/B(C(6)F(5))(3) and [BMIM][PF(6)]/TfOH systems were superior in propargylation with Ib and Ic, while reaction of 3-phenyl-2-propyn-1-ol Id with activated aromatics resulted in the formation of diaryl-propanones instead. Propargylation of anisole with Ib under M(OTf)(3) catalysis is highly para selective, but with TfOH or B(C(6)F(5))(3) as catalyst the ortho isomer was also formed.

Synthesis, crystal and antibacterial studies of diversely functionalized tetrahydropyridin-4-ol.

In an effort to expand the spectrum of antibacterial activity associated with piperidin-4-one derivatives, we have synthesized two series of 3-carboxyethyl-2,6-diphenyl-4-hydroxy-Delta(3)-tetrahydropyridine derivatives bearing diversified heterocyclic and aromatic systems at the nitrogen atom through acetyl (6-18) and 2-propanoyl (9-31) linkers. Unlike acetyl derivatives, NMR spectral pattern of the propanoyl counterparts revealed the existence of pair of rotational isomers (syn and anti) in solution at room temperature due to the hindered rotation about N-CO bond. X-ray crystal studies of 9 and 24 clearly pointed out that all the compounds existed in only one form particularly, in stable syn form in solid state.

Synthesis, stereochemistry and antimicrobial studies of novel oxime ethers of aza/diazabicycles.

Two series of bicyclic oxime ethers viz, 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one O-benzyloximes 13-24 and 2,4,6,8-tetraaryl-3,7-diazabicyclo[3.

Synthesis, spectral, crystal and antimicrobial studies of biologically potent oxime ethers of nitrogen, oxygen and sulfur heterocycles.

Three series of oxime ethers viz, 2,6-diarylpiperidin-4-one O-benzyloximes 5a-o, 2,6-diaryltetrahydropyran-4-one O-benzyloximes 7a-e and 2,6-diaryltetrahydrothiopyran-4-one O-benzyloximes 11a-b and 12a-c were synthesized and stereochemistry is established by their spectral and single crystal analysis. A SAR study has been carried out for the above oxime ethers against a panel of antibacterial (Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhi and Escherichia coli) and antifungal agents (Candida albicans, Candida-51, Rhizopus sp., Aspergillus niger, Aspergillus flavus and Cryptococcus neoformans), respectively, using Ciprofloxacin and Amphotericin B as standards.

A facile synthesis, antibacterial, and antitubercular studies of some piperidin-4-one and tetrahydropyridine derivatives.

The raise in clinical significance of multidrug-resistant bacterial pathogens has directed us to synthesize 2,6-diarylpiperidin-4-one and Delta(3)-tetrahydropyridin-4-ol based benzimidazole and O-arylsulfonyl derivatives. X-ray crystal structure of tetrahydropyridinol (23) confirmed a change in conformation and orientation of substituents upon amide formation. Antibacterial activities evaluated against a wide number of bacterial pathogens (both sensitive and multidrug-resistant) revealed that 19, 27 against Staphylococcus aureus, 27 against Enterococcus faecalis, and 19, 21, 23, and 27 against Enterococcus faecium are significantly good at lowest MIC(90) (16 microg/mL).

1H and 13C NMR spectral assignments of some novel 2,4,6,8-tetraaryl-3,7-diazabicyclo[3.3.1]nonan-9-one derivatives.

The (1)H and (13)C NMR spectra of 2,4,6,8-tetraaryl-3,7-diazabicyclo[3.3.1]nonan-9-ones (1-2), oximes (3-8) and O-benzyl oximes (9-12) were recorded.

Synthesis and biological evaluation of novel benzimidazol/benzoxazolylethoxypiperidone oximes.

Some novel benzimidazol/benzoxazolylethoxypiperidone oximes were synthesized and their antibacterial activity against Staphylococcus aureus (NCIM-2492), Bacillus subtilis (NCIM-2439), Escherichia coli (NCIM-2345) and Pseudomonas aeruginosa (NCIM-2035) and antifungal activity against Candida albicans (NCIM-C27), Candida-6 (NCIM-C27), Candida-51 (NCIM-C27), Aspergillus niger (NCIM-590) and Aspergillus flavus (NCIM-539) have been evaluated. Compounds 26 and 27 exerted potent in vitro antibacterial activity against Bacillus subtilis, Escherichia coli and Staphylococcus aureus while compounds 26, 29 and 30 exhibited potent in vitro antifungal activity against Candida albicans, Candida-51, and Aspergillus niger.