New chalcones and thiopyrimidine analogues derived from mefenamic acid: microwave-assisted synthesis, anti-HIV activity and cytotoxicity as antileukemic agents

Al-Hazam, Hanan A.; Al-Shamkani, Zeki A.; Al‐Masoudi, Najim A.; Saeed, Bahjat A.; Pannecouque, Christophe

doi:10.1515/znb-2016-0223

Cited by 10 publications

(1 citation statement)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The anticancer and antiproliferative activities of chalcones have also been intensively studied against different cancer cell lines [ 16 ]. Their biological activities are due to their chemical structure and α , β -unsaturated carbonyl derivatives [ 17 ]. The most striking is that chalcones do not induce undesirable genotoxic effects as done with many useful anticancer drugs that may interact with the amino groups of purine and pyrimidine nucleotides of nucleic acids [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Anticancer Assessment, and Molecular Docking of Novel Chalcone‐Thienopyrimidine Derivatives in HepG2 and MCF‐7 Cell Lines

Safwat

Hassanin

Mohammed

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Heterocycles containing thienopyrimidine moieties have attracted attention due to their interesting biological and pharmacological activities. In this research article, we reported the synthesis of a series of new hybrid molecules through merging the structural features of chalcones and pyridothienopyrimidinones. Our results indicated that the synthesis of chalcone-thienopyrimidine derivatives from the corresponding thienopyrimidine and chalcones proceeded in a relatively short reaction time with good yields and high purity. Most of these novel compounds exhibited moderate to robust cytotoxicity against HepG2 and MCF-7 cancer cells similar to that of 5-fluorouracil (5-FU). The results indicated that IC50 of the two compounds (3b and 3g) showed more potent anticancer activities against HepG2 and MCF-7 than 5-FU. An MTT assay and flow cytometry showed that only 3b and 3g had anticancer activity and antiproliferative activities at the G1 phase against MCF-7 cells, while six compounds (3a-e and 3g) had cytotoxicity and cell cycle arrest at different phases against HepG2 cells. Their cytotoxicity was achieved through downregulation of Bcl-2 and upregulation of Bax, caspase-3, and caspase-9. Although all tested compounds increased oxidative stress via increment of MDA levels and decrement of glutathione reductase (GR) activities compared to control, the 3a, 3b, and 3g in HepG2 and 3b and 3g in MCF-7 achieved the target results. Moreover, there was a positive correlation between cytotoxic efficacy of the compound and apoptosis in both HepG2 ( R 2 = 0.531 ; P = 0.001 ) and MCF-7 ( R 2 = 0.219 ; P = 0.349 ) cell lines. The results of molecular docking analysis of 3a-g into the binding groove of Bcl-2 revealed relatively moderate binding free energies compared to the selective Bcl-2 inhibitor, DRO. Like venetoclax, compounds 3a-g showed 2 violations from Lipinski’s rule. However, the results of the ADME study also revealed higher drug-likeness scores for compounds 3a-g than for venetoclax. In conclusion, the tested newly synthesized chalcone-pyridothienopyrimidinone derivatives showed promising antiproliferative and apoptotic effects. Mechanistically, the compounds increased ROS production with concomitant cell cycle arrest and apoptosis. Therefore, regulation of the cell cycle and apoptosis are possible targets for anticancer therapy. The tested compounds could be potent anticancer agents to be tested in future clinical trials after extensive pharmacodynamic, pharmacokinetic, and toxicity profile investigations.

show abstract

Section: Introductionmentioning

confidence: 99%

Synthesis, Anticancer Assessment, and Molecular Docking of Novel Chalcone‐Thienopyrimidine Derivatives in HepG2 and MCF‐7 Cell Lines

Safwat

Hassanin

Mohammed

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

Deciphering the enigmas of non‐nucleoside reverse transcriptase inhibitors (NNRTIs): A medicinal chemistry expedition towards combating HIV drug resistance

Zhang,

et al. 2024

Medicinal Research Reviews

View full text Add to dashboard Cite

The pivotal involvement of reverse transcriptase activity in the pathogenesis of the progressive HIV virus has stimulated gradual advancements in drug discovery initiatives spanning three decades. Consequently, nonnucleoside reverse transcriptase inhibitors (NNRTIs) have emerged as a preeminent category of therapeutic agents for HIV management. Academic institutions and pharmaceutical companies have developed numerous NNRTIs, an essential component of antiretroviral therapy. Six NNRTIs have received Food and Drug Administration approval and are widely used in clinical practice, significantly improving the quality of HIV patients. However, the rapid emergence of drug resistance has limited the effectiveness of these medications, underscoring the necessity for perpetual research and development of novel therapeutic alternatives. To supplement the existing literatures on NNRTIs, a comprehensive review has been compiled to synthesize this extensive dataset into a comprehensible format for the medicinal chemistry community. In this review, a thorough investigation and meticulous analysis were conducted on the progressions achieved in NNRTIs within the past 8 years (2016–2023), and the experiences and insights gained in the development of inhibitors with varying chemical structures were also summarized. The provision of a crucial point of reference for the development of wide‐ranging anti‐HIV medications is anticipated.

show abstract

Microwave-assisted synthesis, antiproliferative, antibacterial activities, in silico, computational studies and molecular dynamics simulation of new bis-(aryl-based chalcone) derivatives

Al-Kaabi,

Al-Hazam,

Al-Maliki

et al. 2025

Journal of Molecular Structure

View full text Add to dashboard Cite

New chalcones and thiopyrimidine analogues derived from mefenamic acid: microwave-assisted synthesis, anti-HIV activity and cytotoxicity as antileukemic agents

Cited by 10 publications

References 34 publications

Synthesis, Anticancer Assessment, and Molecular Docking of Novel Chalcone‐Thienopyrimidine Derivatives in HepG2 and MCF‐7 Cell Lines

Synthesis, Anticancer Assessment, and Molecular Docking of Novel Chalcone‐Thienopyrimidine Derivatives in HepG2 and MCF‐7 Cell Lines

Deciphering the enigmas of non‐nucleoside reverse transcriptase inhibitors (NNRTIs): A medicinal chemistry expedition towards combating HIV drug resistance

Microwave-assisted synthesis, antiproliferative, antibacterial activities, in silico, computational studies and molecular dynamics simulation of new bis-(aryl-based chalcone) derivatives

Contact Info

Product

Resources

About