Two new classes of hybrid quinoline-imidazole/benzimidazole derivatives (the hybrid QIBS salts and QIBC cycloadducts) were designed and synthesized to evaluate their anticancer and antimicrobial ...activity. The strategy adopted for synthesis is straight and efficient, in four steps: N-acylation, N-alkylation, quaternization and a Huisgen 3 + 2 cycloaddition. The in vitro single-dose anticancer assay of forty six hybrid quinoline-benzimidazole compounds reveal that one QIBS salt (11h), has an excellent quasi nonselective activity against all type of cancer cell with an excellent PGI in the area of 90-100% and very good lethality. Three others quinoline-imidazole/benzimidazole hybrids (8h, 12h, 12f) has an excellent selective activity against some cancer cell lines: breast cancer MDA-MB-468 and Leukemia HL-60 TB). The five-dose assay screening confirms that compound 11h possesses excellent anti-proliferative activity, with GI
in the range of nano-molar, against some cancer cell lines: Leukemia HL-60 TB, Leukemia K-526, Leukemia RPMI-8226, Breast cancer MDA-MB-468, Lung cancer HOP-92 and Ovarian cancer IGROV1. The antibacterial assay indicates that three hybrid QIBS salts (12f, 12c, 12d) have an excellent activity against Gram-negative bacteria E. coli (superior to control Gentamicin) while against Gram-positive bacteria S. aureus only one compound 8i (R
= -CF3) exhibits a significant activity (superior to control Gentamicin). The MIC assay indicates that two other compounds (11h, 12h) are biologically active to a very low concentration, in the range of nano-molar. We believe that all these excellent assets related to anticancer and antibacterial activities, make from our hybrid quinoline-imidazole/benzimidazole compounds bearing a phenyl group (R
= -C
H
) in the para (4)-position of the benzoyl moiety a good candidate for future drug developing.
We present herein a straightforward and efficient pathway for the synthesis of pyrrolophthalazine cycloadducts via Huisgen 3 + 2 dipolar cycloaddition reactions of phthalazinium ylides to methyl ...propiolate or dimethyl acetylenedicarboxylate (DMAD). A thoroughly comparative study concerning the efficiency of synthesis, conventional thermal heating (TH) versus microwave (MW) and ultrasound (US) irradiation, has been performed. The cycloaddition reactions of phthalazinium ylides to methyl propiolate occur regiospecific, with a single regioisomer being obtained. Under conventional TH, the cycloaddition reaction of phthalazinium ylides with DMAD occurs to a mixture of inseparable partial and fully aromatized pyrrolophthalazine cycloadducts, while MW or US irradiation are leading only to fully aromatized compounds, with the reactions becoming selective. A feasible mechanism for formation of fully aromatized compounds is presented. Besides selectivity, it has to be noticed that the reaction setup under MW or US irradiation offer a number of other certain advantages: higher yields, decreasing of the amount of used solvent comparative with TH, decreasing of the reaction time from hours to minutes and decreasing of the consumed energy; consequently, these reactions could be considered environmentally friendly.
This study presents the synthesis, structural characterization, and in vitro evaluation of anticancer activity of some newly benzo
quinoline derivatives. The synthesis is facile and efficient, ...involving two steps: quaternization of nitrogen heterocycle followed by a 3+2 dipolar cycloaddition reaction. The synthesized compounds were characterized by FTIR, NMR, and X-ray diffraction on monocrystal in the case of compounds
and
. An in vitro single-dose anticancer assay of eighteen benzo
quinoline compounds, quaternary salts, and cycloadducts, was performed. The results showed that the most active compounds were quaternary salts
and
with aromatic R substituents. Quaternary salt
revealed non-selective activity against all types of cancer cells, while salt
exhibited a highly selective activity against leukemia cells. Compound
also presented remarkable cytotoxic efficiency against four distinct types of cancer cells-namely, non-small cell lung cancer HOP-92, melanoma LOX IMVI, melanoma SK-MEL-5, and breast cancer MDA-MB-468. Compound
was selected for five-dose screening. The study also includes SAR correlations.
Lack of specificity and subsequent therapeutic effectiveness of antimicrobial and antitumoral drugs is a common difficulty in therapy. The aim of this study is to investigate, both by experimental ...and computational methods, the antitumoral and antimicrobial properties of a series of synthesized imidazole-pyridine derivatives. Interaction with three targets was discussed: Dickerson-Drew dodecamer (PDB id 2ADU), G-quadruplex DNA string (PDB id 2F8U) and DNA strain in complex with dioxygenase (PDB id 3S5A). Docking energies were computed and represented graphically. On them, a QSAR model was developed in order to further investigate the structure-activity relationship. Results showed that synthesized compounds have antitumoral and antimicrobial properties. Computational results agreed with the experimental data.
Two new series of hybrid quinoline-sulfonamide complexes (M
: Zn
, Cu
, Co
and Cd
) derivatives (
) were designed, synthesized and tested for their antimicrobial activity. The synthesis is ...straightforward and efficient, involving two steps: acylation of aminoquinoline followed by complexation with metal acetate (Cu
, Co
and Cd
) or chloride (Zn
). The synthesized
compounds were characterized by FTIR and NMR spectroscopy and by X-ray diffraction on single crystal. The
compounds were preliminary screened for their antibacterial and antifungal activity and the obtained results are very promising. In this respect, the hybrid
-(quinolin-8-yl)-4-chloro-benzenesulfonamide cadmium (II), considered as leading structure for further studies, has an excellent antibacterial activity against
(with a diameters of inhibition zones of 21 mm and a minimum inhibitory concentration (MIC) of 19.04 × 10
mg/mL), a very good antibacterial activity against
(with a diameters of inhibition zones of 19 mm and a MIC of 609 × 10
mg/mL), and again an excellent antifungal activity against
(with a diameters of inhibition zones of 25 mm and a MIC of 19.04 × 10
mg/mL).
We report here the synthesis and optical spectral properties of several new pyrrolodiazine derivatives. The luminescent heterocycles were synthesized by 1,3-dipolar cycloaddition reactions between ...N-alkylated pyridazine and methylpropiolate or dimethyl acetylenedicarboxylate (DMAD). The pyrrolopyridazine derivatives are blue emitters with moderate quantum yields (around 25%) in the case of pyrrolopyridazines and negligible yet measurable emission for pyrrolophthalazines. In a subsequent step towards including the pyrrolodiazine moiety, given its spectral properties in various macromolecular frameworks such as biological molecules, a subset of the synthetized compounds has been subjected to α-bromination. A selective and efficient way for α-bromination in heterogeneous catalysis of pyrrolodiazine derivatives under microwave (MW) irradiation is presented. We report substantially higher yields under MW irradiation, whereas the solvent amounts required are at least five-fold less compared to classical heating.
We report here the design, synthesis, experimental and in silico evaluation of the antibacterial and antifungal activity of some new benzofquinoline derivatives. Two classes of benzofquinolinium ...derivatives-(benzofquinolinium salts (
) and pyrrolobenzofquinolinium cycloadducts (
)-were designed and obtained in two steps via a direct and facile procedure: quaternization followed by a cycloaddition reaction. The synthesized compounds were characterized by elemental and spectral analysis (FT-IR,
H-NMR,
C-NMR). The antimicrobial assay reveals that the
salts have an excellent quasi-nonselective antifungal activity against the fungus
(some of them higher that the control drug nystatin) and very good antibacterial activity against the Gram positive bacterium
. The
compounds are inactive. Analysis of the biological data reveals interesting SAR correlations in the benzofquinolinium series of compounds. The in silico studies furnished important data concerning the pharmacodynamics, pharmacokinetics and ADMET parameters of the
salts. Studies of the interaction of each
salt
with ATP synthase in the formed complex, reveal that salts
,
and
have the best fit in a complex with ATP synthase. Study of the interaction of each
salt
with TOPO II in the formed complex reveals that salts
and
have the best-fit in complex with TOPO II. The in silico ADMET studies reveal that the
salts have excellent drug-like properties, including a low toxicity profile. Overall, the experimental and in silico studies indicate that compounds
and
(from the aliphatic series), respectively, and
,
and
(from the aromatic series), are promising leading drug candidates.
We present in this paper a direct and efficient study regarding synthesis and spectral characterization of three series of hybrid quinoline anchored with 4-R-benzenesulfonamide moiety, with potential ...antimicrobial activity, by using ultrasound (US) irradiation and conventional methods (CV). The synthesis pathway is efficient and direct, in two steps: an initial N-acylation of 8-aminoquinoline followed by metal complexation with variously M2+ metals (Cd2+, Co2+, Cu2+, Ni2+, Pd2+, Zn2+). For both type of reactions, N-acylation and complexation, under US irradiations the synthesis have some undeniable advantages: the most relevant being the higher yields, a dramatically decrease for reaction time (with about 150 (one hundred fifty) folds for complexation) comparative with conventional methods (CV) (therefore the spent energy decrease in the same way), a decrease of the amount of used solvents. Taking into account the above considerations these reactions setup could be appreciated as eco-friendly. The structures of the obtained hybrid quinoline – sulfonamide complexes (HQBSM) were determined by elemental analysis and by using spectral investigations: FT-IR, NMR experiments, and X-ray diffraction (in three cases). The FT-IR and NMR spectra of complexes show a similar spectroscopic pattern for all complexes and fully confirm the proposed structures. The X-ray spectra analyses prove without doubts the structure of metal complexes, indicating that their structure depends essentially by two factors: the nature of metal and the nature of sulfonamide-quinoline moieties. Complexes containing 4-methoxy-benzoyl moiety and Zn2+ (e.g. 6a) are tetra-coordinated while in the Ni2+ complex (e.g. 6e) the metallic ion forms a distorted square-based bi-pyramid. In the complexes containing 4-nitro-benzoyl moiety and Cd2+ (e.g. 5d) the metallic ion forms a triangular bipyramid. The antibacterial and antifungal assay reveal that only hybrid HQBSM complex (4e) (with 4-chlorophenyl moiety and Ni2+ in molecule) have a significant antibacterial activity.
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•New hybrids with quinoline-benzenesulfonamide structure.•Ultrasound assisted synthesis of quinoline-benzenesulfonamide complexes.•Environmentally friendly synthesis of new complexes with Cd2+, Co2+, Cu2+, Ni2+, Pd2+, Zn2+.•Ni2+ complex forms a distorted square-based bi-pyramid.•Cd2+ complex as a triangular bipyramid.
We report here the design and synthesis of a new hybrid bis-anthracene-imidazolium salt, having a pyridine scaffold. NMR studies of dimer generation, as well as complexation with zinc acetate were ...performed.
The design, synthesis, structure, and in vitro anticancer and antimycobacterial activity of new hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives are described. The strategy adopted ...for synthesis is straight and efficient, involving a three-step setup procedure: N-acylation, N-alkylation, and quaternization of nitrogen heterocycle. The solubility in microbiological medium and anticancer and antimycobacterial activity of a selection of new synthesized compounds were evaluated. The hybrid derivatives have an excellent solubility in microbiological medium, which make them promising from the pharmacological properties point of view. One of the hybrid compounds, 9 (with a benzimidazole and 8-aminoquinoline skeleton), exhibits a very good and selective antitumor activity against Renal Cancer A498 and Breast Cancer MDA-MB-468. Moreover, the anticancer assay suggests that the hybrid Imz (Bimz)/2-AP (8-AQ) compounds present a specific affinity to Renal Cancer A498. Concerning the antimycobacterial activity, only the hybrid compound, 9, has a significant activity. SAR correlations have been performed.
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