462067-00-1Relevant articles and documents
The antimicrobial potential and pharmacokinetic profiles of novel quinoline-based scaffolds: synthesis andin silicomechanistic studies as dual DNA gyrase and DHFR inhibitors
Abulkhair, Hamada S.,Ahmed, Hany E. A.,Al-Karmalamy, Ahmed A.,Alswah, Mohamed,Bayoumi, Ashraf H.,El-Adl, Khaled,El-Gamal, Kamal M.,El-Shershaby, Mohamed H.
, p. 13986 - 14004 (2021/08/16)
The resistance of pathogenic microbes to currently available antimicrobial agents has been considered a global alarming concern. Hence, close attention should be paid to the development of novel potent antimicrobials. Herein, we report the synthesis,in vitroantimicrobial evaluation, of two novel sets of quinoline derivatives as potential DNA gyrase and DHFR inhibitors. The design of new compounds depended on modifying the structural aspects of previously reported fluoroquinolones. In both sets, the methyl group replaced the fluorine atom at C-6. In the first set, the diverse heterocyclic fragments of reported antimicrobial potentials, including pyrazole, isoxazole, and pyrimidine, were attached to C-3 of the quinoline scaffold. In the second set, the quinolone ring was replaced with the pyrazolo[3,4-b]quinoline scaffold to examine the effect of this action on the antimicrobial activity and thein silicovirtual binding with DNA gyrase and DHFR. The preliminary antimicrobial activity of new compounds was assessed against a panel of pathogenic microbes including Gram-positive bacteria (Streptococcus pneumoniaandBacillus subtilis), Gram-negative bacteria (Pseudomonas aeruginosaandEscherichia coli), and fungal strains (Aspergillus fumigatus,Syncephalastrum racemosum, andGeotriucum candidum). Six derivatives displayed relatively potent antimicrobial activity with a percent activity range of 80-113% relative to ampicillin, gentamicin, and amphotericin B as reference antimicrobial agents. Molecular docking studies were conducted to predict the binding affinities of new compounds toward the active sites of DNA gyrase and DHFR as proposed therapeutic targets.
lH-Pyrazolo[3,4-b]quinolin-3-amine derivatives inhibit growth of colon cancer cells via apoptosis and sub G1 cell cycle arrest
Karthikeyan, Chandrabose,Amawi, Haneen,Viana, Arabela Guedes,Sanglard, Leticia,Hussein, Noor,Saddler, Maria,Ashby, Charles R.,Moorthy, N.S. Hari Narayana,Trivedi, Piyush,Tiwari, Amit K.
, p. 2244 - 2249 (2018/05/31)
A series of lH-pyrazolo[3,4-b]quinolin-3-amine derivatives were synthesized and evaluated for anticancer efficacy in a panel of ten cancer cell lines, including breast (MDAMB-231 and MCF-7), colon (HCT-116, HCT-15, HT-29 and LOVO), prostate (DU-145 and PC3), brain (LN-229), ovarian (A2780), and human embryonic kidney (HEK293) cells, a non-cancerous cell line. Among the eight derivatives screened, compound QTZ05 had the most potent and selective antitumor efficacy in the four colon cancer cell lines, with IC50 values ranging from 2.3 to 10.2 μM. Furthermore, QTZ05 inhibited colony formation in HCT-116 cells in a concentration-dependent manner. Cell cycle analysis data indicated that QTZ05 caused an arrest in the sub G1 cell cycle in HCT-116 cells. QTZ05 induced apoptosis in HCT-116 cells in a concentration-dependent manner that was characterized by chromatin condensation and increase in the fluorescence of fluorochrome-conjugated Annexin V. The findings from our study suggest that QTZ05 may be a valuable prototype for the development of chemotherapeutics targeting apoptotic pathways in colorectal cancer cells.
Pyrazolo-fused quinoline analogues: Synthesis of 1H-pyrazolo [3, 4-b] quinolines and 3-amino-1H-pyrazolo [3, 4-b] quinolines from 3-formyl and 3-cyano-2-chloroquinolines
Srivastava, Ambika,Singh, Mrityunjay K.,Singh
, p. 292 - 296 (2007/10/03)
Stepwise synthesis of 1H-pyrazolo [3, 4-b] quinolines 6 has been described from the reactions of 2-chloro-3-formylquinolines 1 with ethyleneglycol and hydrazine hydrate reagents in sequence followed by hydrolysis with BiCl 3. However, 3-amino-1H-pyrazolo[3, 4-b]quinolines 7 have been synthesized from 2-chloro-3-cyanoquinolines 2 with excess of hydrazine hydrate in one step. The functional group manipulation of amino group in compounds 7 has also been studied.
