Abstract:A new series quinoline‐2H‐1,2,4‐triazol‐3(4H)‐ones 7 g‐n and 11 g‐n were designed and synthesized. Docking studies of title compounds with DNA (PDB: 1AU5) and with long‐chain enoyl‐acyl carrier protein reductase (InhA) enzyme (PDB ID: 4TZK) as anticancer and antitubercular targets showed good insights on the possible interactions. Further, the compounds were tested for in vitro anticancer activity against HeLa human cervix tumor cell line and also in vitro antitubercular activity against M. tuberculosis H37Rv … Show more
“…All starting materials were weighed and handled in air at room temperature. Precursor quinolone derivatives ( 8 ( a – c )) [ 67 ] and 4-aryl-2-chloropyrimidines ( 1 – 4 ) [ 58 ] were prepared according to reported procedures.…”
Section: Methodsmentioning
confidence: 99%
“…All starting materials were weighed and handled in air at room temperature. Precursor quinolone derivatives (8(a-c)) [67] and 4-aryl-2-chloropyrimidines (1-4) [58] were prepared according to reported procedures. 3-(Bromomethyl)-2-chloroquinoline (0.30 mmol) was added to a solution of 5 (0.30 mmol) and potassium carbonate (0.60 mmol) in acetonitrile (5mL).…”
A battery of novel pyrimidine-quinolone hybrids was designed by docking scaffold replacement as lactate dehydrogenase A (hLDHA) inhibitors. Structures with different linkers between the pyrimidine and quinolone scaffolds (10-21 and 24–31) were studied in silico, and those with the 2-aminophenylsulfide (U-shaped) and 4-aminophenylsulfide linkers (24–31) were finally selected. These new pyrimidine-quinolone hybrids (24–31)(a–c) were easily synthesized in good to excellent yields by a green catalyst-free microwave-assisted aromatic nucleophilic substitution reaction between 3-(((2/4-aminophenyl)thio)methyl)quinolin-2(1H)-ones 22/23(a–c) and 4-aryl-2-chloropyrimidines (1–4). The inhibitory activity against hLDHA of the synthesized hybrids was evaluated, resulting IC50 values of the U-shaped hybrids 24–27(a–c) much better than the ones of the 1,4-linked hybrids 28–31(a–c). From these results, a preliminary structure–activity relationship (SAR) was established, which enabled the design of novel 1,3-linked pyrimidine-quinolone hybrids (33–36)(a–c). Compounds 35(a–c), the most promising ones, were synthesized and evaluated, fitting the experimental results with the predictions from docking analysis. In this way, we obtained novel pyrimidine-quinolone hybrids (25a, 25b, and 35a) with good IC50 values (<20 μM) and developed a preliminary SAR.
“…All starting materials were weighed and handled in air at room temperature. Precursor quinolone derivatives ( 8 ( a – c )) [ 67 ] and 4-aryl-2-chloropyrimidines ( 1 – 4 ) [ 58 ] were prepared according to reported procedures.…”
Section: Methodsmentioning
confidence: 99%
“…All starting materials were weighed and handled in air at room temperature. Precursor quinolone derivatives (8(a-c)) [67] and 4-aryl-2-chloropyrimidines (1-4) [58] were prepared according to reported procedures. 3-(Bromomethyl)-2-chloroquinoline (0.30 mmol) was added to a solution of 5 (0.30 mmol) and potassium carbonate (0.60 mmol) in acetonitrile (5mL).…”
A battery of novel pyrimidine-quinolone hybrids was designed by docking scaffold replacement as lactate dehydrogenase A (hLDHA) inhibitors. Structures with different linkers between the pyrimidine and quinolone scaffolds (10-21 and 24–31) were studied in silico, and those with the 2-aminophenylsulfide (U-shaped) and 4-aminophenylsulfide linkers (24–31) were finally selected. These new pyrimidine-quinolone hybrids (24–31)(a–c) were easily synthesized in good to excellent yields by a green catalyst-free microwave-assisted aromatic nucleophilic substitution reaction between 3-(((2/4-aminophenyl)thio)methyl)quinolin-2(1H)-ones 22/23(a–c) and 4-aryl-2-chloropyrimidines (1–4). The inhibitory activity against hLDHA of the synthesized hybrids was evaluated, resulting IC50 values of the U-shaped hybrids 24–27(a–c) much better than the ones of the 1,4-linked hybrids 28–31(a–c). From these results, a preliminary structure–activity relationship (SAR) was established, which enabled the design of novel 1,3-linked pyrimidine-quinolone hybrids (33–36)(a–c). Compounds 35(a–c), the most promising ones, were synthesized and evaluated, fitting the experimental results with the predictions from docking analysis. In this way, we obtained novel pyrimidine-quinolone hybrids (25a, 25b, and 35a) with good IC50 values (<20 μM) and developed a preliminary SAR.
“…Nine quinoline derivatives were synthesized according to the procedure reported elsewhere [ 26 ]. The IUPAC naming, molecular weight, and the codes for these compounds are given in Table 1 .…”
Section: Methodsmentioning
confidence: 99%
“…1(B) ) are shown to possess inhibitory effect on phosphodiesterases (PDEs) [ 25 ]. Since inhibition of PDEs in spermatozoa can enhance the motility, we were interested in assessing whether the novel quinoline derivatives synthesized by our group [ 26 ] have any significant beneficial effect on motility and other physiological properties in human spermatozoa. Fig.…”
In this study, we aimed to explore the beneficial properties of novel quinoline derivatives on human sperm motility and its functional competence. Nine novel quinoline derivatives were screened for their effect on motility in human spermatozoa from normozoospermic ejaculates. Compounds with impressive sperm motility enhancement properties were further assessed for their effect on functional competence of human spermatozoa. To determine the effect on the fertilizing ability of spermatozoa processed with quinoline derivatives and to assess developmental competence of embryos derived, in vitro fertilization (IVF) was performed using mouse model. Among the nine quinoline derivatives, 2 compounds (6MQT and 2,6DQT) exhibited significant enhancement in sperm progressive motility and survival at 24 h. Further, non-significant increase in curvilinear velocity (VCL), straight line velocity (VSL), and amplitude of lateral head displacement (ALH) was observed. Capacitation, intracellular cAMP level and tyrosine phosphorylated sperm proteins were significantly higher in 6MQT (P < 0.05) and 2,6DQT (P < 0.001) compared to control. In vitro fertilization (IVF) experiments using Swiss albino mice revealed that spermatozoa processed with 6MQT had non-significantly higher blastocyst rate and a superior blastocyst quality, while, 2,6DQT resulted in significantly lower blastocyst rate (P < 0.05) compared to control. Quinoline derivative 6MQT has significant motility enhancement property under in vitro conditions.
“…During the course of our studies directed toward the design and synthesis of heterocycles employing a ring transformation of sydnones, we have recently reported the newer heterocyclic scaffolds using 3-arylsydnones 1a–d as synthons. − We, herein, report the serendipitous formation of pyrazolo[3,4- d ]pyridazin-7(6 H )-ones ( 7a–l ) from hydrazone of 3-aryl-4-acetylsydnones 2a–d by intramolecular nucleophilic addition–elimination. The synthetic route for the synthesized compounds is outlined in Scheme .…”
Fused
nitrogen heterocyclesnamely, pyrazolo[3,4-
d
]pyridazin-7(6
H
)-ones have been obtained by
exploiting the 1,3-dipolar nature of
N
-arylsydnones,
from hydrazones of 3-aryl-4-acetylsydnones
via
the
Vilsmeier–Haack strategy. Facile intramolecular nucleophilic
addition followed by CO
2
elimination under reflux or upon
microwave irradiation was presented. Plausible mechanisms for the
formation of the title compounds are proffered. Structure confirmatory
evidence came from single-crystal X-ray crystallography.
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