Łukasz Kaczmarek

Mild and Efficient Conversion of Nitriles to Amides with Basic Urea-Hydrogen Peroxide Adduct

Abstract The urea-hydrogen peroxide adduct, an inexpensive, stable and easily handled reagent has shown utility for mild and efficient transformation of nitriles into the corresponding aliphatic or aromatic amides. Reaction proceeds in aqueous acetone, within 0.5-2.5h, in the presence of catalytic amount of K2CO3, at room temperature.

Strongly modified [2,2′-bipyridyl]-3,3′-diol (BP(OH)2): a system undergoing excited state intramolecular proton transfer as a photostabilizer of polymers and as a solar energy collector

Abstract Six new compounds, derivatives of [2,2′-bipyridyl]-3,3′-diol (BP(OH) 2 ) are recommended as useful modifications of the parent structure. One group, three molecules with conjugate aromatic substituents (6-methyl-6′-styryl-BP(OH) 2 , 6-(4-methoxystyryl)-6′-methyl-BP(OH) 2 , 6-methyl-6′-(4-phenylstyryl)-BP(OH) 2 ), are potential solar energy concentrators — they have absorption spectra red shifted with respect to BP(OH) 2 . To the second group belong the derivatives with the aliphatic side chains, better “accepted” by polyethylene than the parent molecule. These compounds are designed to improve their function as photostabilizers of polymers. All six new compounds were synthesized and their photophysical characteristics were studied. Absorption spectra, phototautomeric fluorescences and their excitation spectra, as well as quantum yields and lifetimes are reported.

New proton transfer lasing systems—derivatives of 2,2′-bipyridyl. Synthesis and photophysical characteristics

Abstract Two new bipyridyl derivatives undergoing the excited state intramolecular proton transfer were synthesized: 5-methyl-[2,2′-bipyridine]-3,3′-diol and 5,5′-dimethyl-[2,2′-bipyridine]-3,3′-diol. Both reveal a strong phototautomeric, largely Stokes-shifted fluorescence and can be used as proton transfer laser dyes. Tuning ranges and lasing efficiences are also reported.

Synthesis and biological evaluation of new amino acid and dipeptide derivatives of neocryptolepine as anticancer agents.

The syntheses of neocryptolepine derivatives containing an amino acid or a dipeptide at the C-9 position and their evaluation for antitumor activity in vitro and in vivo are reported. To establish the influence of an amino acid or a peptide on the physicochemical properties of 5H-indolo[2,3-b]quinoline (DiMIQ), lipophilic and hemolytic properties were investigated. Most of the compounds displayed a high antiproliferative activity in vitro and strongly inhibited growth of tumor in mice compared to cyclophosphamide. The attachment of the hydrophilic amino acid or the peptide to the hydrophobic DiMIQ increased its hydrophilic properties and decreased its hemolytic activity. The glycylglycine conjugate (7a) was the most promising derivative. It strongly inhibited the growth of the tumor in mice (at dose 50 mg kg(-1) day(-1) it inhibited the tumor growth by 46-63% on days 11-16 and by 29-43% on days 18-23) and significantly decreased hemolytic activity and lowered the in vivo toxicity compared to DiMIQ.

Cytotoxicity and cell cycle effects of novel indolo[2,3-b]quinoline derivatives

Cellular effects of novel indolo[2,3-b]quinoline derivatives were studied. These compounds are synthetic analogs of plant alkaloid neocryptolepine (5-methyl-5H-indolo[2,3-b]quinoline) present in extracts from Cryptolepis sanguinolenta. They are traditionally used in natural medicine in Central and West Africa. Previous molecular and computational studies indicated that these compounds were DNA intercalators and inhibitors of topoisomerase II. We have extended our studies on their mode of action to the cellular level. Past experiments have shown that these compounds were active in vitro against cell lines derived from solid tumors, so for the present studies we selected leukemic cell lines. Jurkat acute T cell, CCRF-CEM T lymphoblastoid, THP-1 acute monocytic, HL-60 acute promyelocytic leukemias, and HL-60/MX2 subline with reduced expression of topoisomerase II were used. We evaluated the cytotoxicity and cell cycle effects of the indolo[2,3-b]quinoline compounds. We also tested if these compounds were able to induce apoptosis in the cells. Our studies revealed that novel indolo[2,3-b]quinoline derivatives were more cytotoxic to all cell lines than etoposide (used as a reference topoisomerase II inhibitor), and that their cytotoxicity depended on the substituents introduced to the indolo[2,3-b]quinoline core. Surprisingly, our studies have shown that HL-60/MX2 cell line and also THP-1 cell line, resistant to etoposide, were susceptible to methyl- and methoxy-substituted indolo[2,3-b]quinoline derivatives. In parallel to the evaluation of cytotoxicity we studied cell cycle effects of these compounds. Treatment of HL-60 cells with etoposide in subcytotoxic concentrations resulted in a massive accumulation of the cells in the G2/M phase of the cell cycle. When we used subcytotoxic concentrations of our novel indolo[2,3-b]quinoline derivatives the cell cycle progression of HL-60 cells was not affected. Moreover, the cell cycle of HL-60/MX2 cells was not influenced by any of the compounds studied. Indolo[2,3-b]quinoline derivatives induced apoptosis in HL-60 and HL-60/MX2 cells, but only in concentrations close to IC50 determined in cytotoxic assays. Etoposide induced apoptosis in HL-60 parental cell line, but in a very broad range of concentrations. Our results suggest that topoisomerase II may not represent the main cellular target for novel indolo[2,3-b]quinoline derivatives. They show that the cells resistant to topoisomerase II poison, etoposide, were still sensitive to our compounds.

Searching for new derivatives of neocryptolepine: Synthesis, antiproliferative, antimicrobial and antifungal activities

A series of novel amino acid and dipeptide derivatives of neocryptolepine were synthesized and tested for their antimicrobial, antifungal and antiproliferative activity in vitro against cancer cell lines (KB, A549, MCF-7, LoVo) and normal mice fibroblast cells (BALB/3T3). Biological evaluation revealed that almost all of the new compounds displayed high antiproliferative activity against the tested cells and moderate to potent antibacterial activities. Interestingly, these compounds were active against Candida albicans biofilms at doses significantly lower than those required against free-floating planktonic fungal cells. The most promising compounds are derivatives with glycine and L-proline as a substituent both at 2 and at 9 position of 5H-indolo[2,3-b]quinoline. In general, these new compounds (2a, 3a, 6a and 7a) showed the highest dual action against cancer lines and infectious pathogenic microbes in vitro.

Synthesis and NMR study of new derivatives of [2,2′-bipyridyl]-3,3′-diol and [2,2′-bipyridyl]-3-ol

Abstract Seven compounds, forming intramolecular hydrogen bonds, mostly non-symmetric derivatives of [2,2′-bipyridyl]-3,3′-diol (BP(OH)2) were synthesised. Six of them were chosen for the further analysis. It was proved that the electron-donating (CH3) or electron withdrawing (COOH, COOCH3) substituent introduced next to the reactive proton transfer site (N-atom) may change the parameters of hydrogen bridge in a predictable way. The ab initio (GIAO-CHF/DZP//6-31 G∗∗) and semiempirical (PM3) calculations of the ground state were performed. The molecular geometries, Mulliken net charges, NMR shielding constants were compared with some experimental data. In particular, the 15N nuclear magnetic resonance was used to compare the strength of two internal H-bonds of the molecule.

An NMR study of hydrogen bonding in (2, 2′-bipyridyl)-3,3′-diol and related compounds

Abstract It is clearly demonstrated that a combination of 15N and 17O NMR measurements provides an insight into the presence and extent of intramolecular hydrogen bond formation between phenol oxygen atoms and pyridyl nitrogen atoms.

13C NMR studies on the structure of 5H- and 6H-indolo-[2,3-b]quinolines and the related compounds

Abstract A set of 13 C NMR data which included one-bond spin–spin coupling constants has been obtained for a large series of heteroaromatic compounds. It contains, among others, 6-substituted quinolines, their N -oxides, 2- and 5-methoxyindoles. The results obtained for these basic molecules were compared with those measured for a series of variously substituted 5 H - and 6 H -indolo[2,3- b ]quinolines, which shed new light on the electronic structure of the two latter groups of the compounds.

1 H and 13C NMR studies of 6,11-dimethyl-6H-indolo[2,3-b] quinoline and some of its derivatives

The 1H and 13C NMR spectra of the parent 6,11-dimethyl-6H indolo[2,3-b]quinoline and of its nine 2- and 9- methyl-, methoxy- and fluoro-substituted derivatives have been measured and analysed by the use of cosy, HETCOR, SPT INEPT and selective decoupling experiments. The INADEQUATE experiment was applied to yield the one-bond 13C–13C coupling constants for most of the compounds studied. Proton–proton coupling constants including long-range ones have also been determined. Strong concentration effects on the spectra have been observed for all the compounds studied. In particular, large upheld shifts upon the increase of concentration have been observed for some proton resonances. This has been explained in terms of self association of the compounds.