Quinazolines and anticancer activity: A current perspectives

Rahman, Mujeeb Ur; Jeyabalan, G.; Saraswat, Pankaj; Parveen, Gazala; Khan, Sajjad Ahmad; Yar, Mohammad Shahar

doi:10.1080/00397911.2016.1269926

Cited by 21 publications

(11 citation statements)

References 82 publications

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“…14 Therefore, quinazolines represent an important scaffold to the development of DNA-targeted anticancer agents. 14,16 Pyrimidodiazepines are an important bicyclic system due to their biological activities, 17,18 being a very interesting scaffold in medicinal chemistry, which has been incorporated into many drugs as antitumor 19 and antiviral agents, 20,21 given its ability to mimic the nitrogenous bases of nucleic acids. 17,20 Furthermore, pyrimidodiazepines have shown important activity as Aurora A/B, 22 Fig.…”

Section: Introductionmentioning

confidence: 99%

Anticancer activity of pyrimidodiazepines based on 2-chloro-4-anilinoquinazoline: synthesis, DNA binding and molecular docking

et al. 2021

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Section: Introductionmentioning

confidence: 99%

Anticancer activity of pyrimidodiazepines based on 2-chloro-4-anilinoquinazoline: synthesis, DNA binding and molecular docking

et al. 2021

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“…The anticancer mechanisms underlying apoptosis induction and antiproliferative activity have been previously reported ( 28 ). However, the autophagy-associated mechanisms of action of these compounds, particularly in chemoresistant cancer cells, have not been extensively investigated ( 36 , 37 ). The present study examined the cytotoxic effect of MJ-33 on a chemoresistant CRC cell line.…”

Section: Discussionmentioning

confidence: 99%

Novel quinazolinone MJ‑33 induces AKT/mTOR‑mediated autophagy‑associated apoptosis in 5FU‑resistant colorectal cancer cells

Chiang²,

Tsai

et al. 2020

Oncol Rep

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Novel quinazolinone compounds have been studied in the field of drug discovery for a long time. Among their broad range of pharmacological effects, certain compounds effectively inhibit cancer cell proliferation. MJ-33 is a quinazolinone derivative with proposed anticancer activities that was synthesized in our laboratory. The present study aimed to evaluate the anticancer activity of MJ-33 in fluorouracil (5FU)-resistant colorectal cancer cells (HT-29/5FUR) and to investigate the underlying molecular mechanisms. The cell viability assay results indicated that HT-29/5FUR cell viability was inhibited by MJ-33 treatment in a concentration-dependent manner compared with the control group. The cellular morphological alterations observed following MJ-33 treatment indicated the occurrence of apoptosis and autophagy, as well as inhibition of cell proliferation in a time-dependent manner compared with the control group. The acridine orange, LysoTracker Red and LC3-green fluorescent protein staining results indicated that MJ-33 treatment significantly induced autophagy compared with the control group. The DAPI/TUNEL dual staining results demonstrated increased nuclear fragmentation and condensation following MJ-33 treatment compared with the control group. The Annexin V apoptosis assay and image cytometry analysis results demonstrated a significant increase in apoptotic cells following MJ-33 treatment compared with the control group. The western blotting results demonstrated markedly decreased Bcl-2, phosphorylated (p)-BAD, pro-caspase-9 and pro-caspase-3 expression levels, and notably increased cytochrome c and apoptotic peptidase activating factor 1 expression levels following MJ-33 treatment compared with the control group. Moreover, the expression levels of autophagy-related proteins, including autophagy related (ATG)-5, ATG-7, ATG-12, ATG-16, p62 and LC3-II, were increased following MJ-33 treatment compared with the control group. Furthermore, MJ-33-treated HT-29/5FUR cells displayed decreased expression levels of p-AKT and p-mTOR compared with control cells. The results suggested that MJ-33-induced apoptosis was mediated by AKT signaling, and subsequently modulated via the mitochondria-dependent signaling pathway. Therefore, the results suggested that suppression of AKT/mTOR activity triggered autophagy in the HT-29/5FUR cell line. In summary, the results indicated that MJ-33 inhibited HT-29/5FUR cell viability, and induced apoptosis and autophagy via the AKT/mTOR signaling pathway. The present study may provide novel insight into the anticancer effects and mechanisms underlying MJ-33 in 5FU-resistant colorectal cancer cells.

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“…Functionalized quinazoline and fused quinazolines have long been of increasing interest in the field of synthetic organic and medicinal chemistry on account of the wide range of biologic activities,11–14 including anticancer,15 anti-inflammatory,16 antituberculosis,17 anticonvulsant,18 antimalarial,19 antihypertensive,20 antidiabetic,21 and so on. Furthermore, suitably substituted thiazolo[2,3-b]quinazolines also serve as versatile building blocks in synthetic chemistry.…”

Section: Introductionmentioning

confidence: 99%

“…Thiazole-based heterocycles are central to modern chemical synthesis due to their synthetic feasibility and their incorporation into various types of therapeutically useful agents and are of paramount interest in the development of important pharmacophores in the drug discovery endeavor. 9 , 10 Functionalized quinazoline and fused quinazolines have long been of increasing interest in the field of synthetic organic and medicinal chemistry on account of the wide range of biologic activities, 11 – 14 including anticancer, 15 anti-inflammatory, 16 antituberculosis, 17 anticonvulsant, 18 antimalarial, 19 antihypertensive, 20 antidiabetic, 21 and so on. Furthermore, suitably substituted thiazolo[2,3-b]quinazolines also serve as versatile building blocks in synthetic chemistry.…”

Section: Introductionmentioning

confidence: 99%

<em>p</em>-TSA-promoted syntheses of 5H-benzo[h]thiazolo[2,3-b]quinazoline and indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogs: molecular modeling and in vitro antitumor activity against hepatocellular carcinoma

Keshari¹,

Singh²,

Raj³

et al. 2017

DDDT

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In our efforts to address the rising incidence of hepatocellular carcinoma (HCC), we have made a commitment to the synthesis of novel molecules to combat Hep-G2 cells. A facile and highly efficient one-pot, multicomponent reaction has been successfully devised utilizing a p-toluenesulfonic acid (p-TSA)-catalyzed domino Knoevenagel/Michael/intramolecular cyclization approach for the synthesis of novel 5H-benzo[h]thiazolo[2,3-b]quinazoline and indeno[1,2-d] thiazolo[3,2-a]pyrimidine analogs bearing a bridgehead nitrogen atom. This domino protocol constructed one new ring by the concomitant formation of multiple bonds (C–C, C–N, and C=N) involving multiple steps without the use of any metal catalysts in one-pot, with all reactants effi-ciently exploited. All the newly synthesized compounds were authenticated by means of Fourier transform infrared spectroscopy, liquid chromatography–mass spectrometry, proton nuclear magnetic resonance spectroscopy, and carbon-13 nuclear magnetic resonance spectroscopy, together with elemental analysis, and their antitumor activity was evaluated in vitro on a Hep-G2 human cancer cell line by sulforhodamine B assay. Computational molecular modeling studies were carried out on cancer-related targets, including interleukin-2, interleukin-6, Caspase-3, and Caspase-8. Two compounds (4A and 6A) showed growth inhibitory activity comparable to the positive control Adriamycin, with growth inhibition of 50% <10 μg/mL. The results of the comprehensive structure–activity relationship study confirmed the assumption that two or more electronegative groups on the phenyl ring attached to the thiazolo[2,3-b]quinazoline system showed the optimum effect. The in silico simulations suggested crucial hydrogen bond and π–π stacking interactions, with a good ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile and molecular dynamics, in order to explore the molecular targets of HCC which were in complete agreement with the in vitro findings. Considering their significant anticancer activity, 4A and 6A are potential drug candidates for the management of HCC.

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Quinazolines and anticancer activity: A current perspectives

Cited by 21 publications

References 82 publications

Anticancer activity of pyrimidodiazepines based on 2-chloro-4-anilinoquinazoline: synthesis, DNA binding and molecular docking

Anticancer activity of pyrimidodiazepines based on 2-chloro-4-anilinoquinazoline: synthesis, DNA binding and molecular docking

Novel quinazolinone MJ‑33 induces AKT/mTOR‑mediated autophagy‑associated apoptosis in 5FU‑resistant colorectal cancer cells

<em>p</em>-TSA-promoted syntheses of 5H-benzo[h]thiazolo[2,3-b]quinazoline and indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogs: molecular modeling and in vitro antitumor activity against hepatocellular carcinoma

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