Design, synthesis and cytotoxicity of chimeric erlotinib-alkylphospholipid hybrids

Alam, Md. Golam Rabiul; Hassan, Ahmed H.E.; Lee, Kun Won; Cho, Min Chang; Yang, Jae-Seung; Song, Jang Ho; Min, Kyung Hoon; Hong, Jongki; Kim, Dong-Hyun; Lee, Yong Sup

doi:10.1016/j.bioorg.2018.11.021

Cited by 25 publications

(12 citation statements)

References 51 publications

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“…Thus, compound 6e produced excellent inhibition of the growth of OVCAR-3 and NCI/ ADR-RES cells by 93. 3 9). Herein also compound 6e was the best compound showing promising good inhibition of both PC-3 and DU-145 cells.…”

Section: 233mentioning

confidence: 99%

“…Cancer persists to be a major hurdle to human wellbeing causing the second-highest mortality rate after cardiovascular diseases 1 . Despite the advances in chemotherapeutic approaches, unmet clinical needs maintain cancer as a leading cause of death 2 , 3 . Furthermore, cancer is a group of heterogeneous diseases with multifactorial etiology and inevitability for resistance evolvement.…”

Section: Introductionmentioning

confidence: 99%

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Reprofiling of pyrimidine-based DAPK1/CSF1R dual inhibitors: identification of 2,5-diamino-4-pyrimidinol derivatives as novel potential anticancer lead compounds

Farag

Hassan

Ahn

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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Hybridization of reported weakly active antiproliferative hit 5-amino-4-pyrimidinol derivative with 2-anilino-4-phenoxypyrimidines suggests a series of 2,5-diamino-4-pyrimidinol derivatives as potential antiproliferative agents. Few compounds belonging to the proposed series were reported as CSF1R/DAPK1 inhibitors as anti-tauopathies. However, the correlation between CSF1R/DAPK1 signalling pathways and cancer progression provides motives to reprofile them against cancer therapy. The compounds were synthesised, characterized, and evaluated against M-NFS-60 cells and a kinase panel which bolstered predictions of their antiproliferative activity and suggested the involvement of diverse molecular targets. Compound 6e, the most potent in the series, showed prominent broad-spectrum antiproliferative activity inhibiting the growth of hematological, NSCLC, colon, CNS, melanoma, ovarian, renal, prostate and breast cancers by 84.1, 52.79, 72.15, 66.34, 66.48, 51.55, 55.95, 61.85, and 60.87%, respectively. Additionally, it elicited an IC50 value of 1.97 µM against M-NFS-60 cells and good GIT absorption with Pe value of 19.0 ± 1.1 × 10−6 cm/s (PAMPA-GIT). Molecular docking study for 6e with CSF1R and DAPK1 was done to help to understand the binding mode with both kinases. Collectively, compound 6e could be a potential lead compound for further development of anticancer therapies.

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Section: 233mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reprofiling of pyrimidine-based DAPK1/CSF1R dual inhibitors: identification of 2,5-diamino-4-pyrimidinol derivatives as novel potential anticancer lead compounds

Farag

Hassan

Ahn

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Notably, compound 9 had the best efficacy against MCF-7 cell line than reference erlotinib and miltefosine [ Figure 2 ]. [ 38 ]…”

Section: Anti-cancer Activitiesmentioning

confidence: 99%

Quinazolinone-based hybrids with diverse biological activities: A mini-review

2022

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Quinazolinone and quinazoline have been shown different pharmacological activities, namely anticancer, anti-inflammatory, anti-hyperlipidemia, analgesic, antihypertensive, and antibacterial. On the other hand, molecular hybridization is a structural modification technique in the design of new ligands which consist of two or more pharmacologically active molecules in one structure. Therefore, due to the importance of the biological activities of quinazolinones for the development of new therapeutic agents, this review emphasizes current findings on various quinazolinone-based hybrids in medicinal chemistry. Moreover, it highlights the biological activities and structure-activity relationship of these hybrids.

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“…Herein, the most active compound ( Figure 3 : 23) showed higher efficacy than the reference erlotinib and miltefosine. Statistical correlation analysis indicates that both mechanisms (EGFR kinase and Akt phosphorylation inhibition) have an influence on the cytotoxic effect of compounds towards human cancer cells ( Alam et al, 2019 ).…”

Section: Antitumor Effects Of Quinazoline Derivativesmentioning

confidence: 99%

Quinazoline Derivatives as Potential Therapeutic Agents in Urinary Bladder Cancer Therapy

et al. 2021

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Cancer diseases remain major health problems in the world despite significant developments in diagnostic methods and medications. Many of the conventional therapies, however, have limitations due to multidrug resistance or severe side effects. Bladder cancer is a complex disorder, and can be classified according to its diverse genetic backgrounds and clinical features. A very promising direction in bladder cancer treatment is targeted therapy directed at specific molecular pathways. Derivatives of quinazolines constitute a large group of chemicals with a wide range of biological properties, and many quinazoline derivatives are approved for antitumor clinical use, e.g.,: erlotinib, gefitinib, afatinib, lapatinib, and vandetanib. The character of these depends mostly on the properties of the substituents and their presence and position on one of the cyclic compounds. Today, new quinazoline-based compounds are being designed and synthesized as potential drugs of anticancer potency against bladder cancers.

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Design, synthesis and cytotoxicity of chimeric erlotinib-alkylphospholipid hybrids

Cited by 25 publications

References 51 publications

Reprofiling of pyrimidine-based DAPK1/CSF1R dual inhibitors: identification of 2,5-diamino-4-pyrimidinol derivatives as novel potential anticancer lead compounds

Reprofiling of pyrimidine-based DAPK1/CSF1R dual inhibitors: identification of 2,5-diamino-4-pyrimidinol derivatives as novel potential anticancer lead compounds

Quinazolinone-based hybrids with diverse biological activities: A mini-review

Quinazoline Derivatives as Potential Therapeutic Agents in Urinary Bladder Cancer Therapy

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