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Haematological problems
Published in Catherine Nelson-Piercy, Handbook of Obstetric Medicine, 2020
Outside pregnancy cytotoxic agents such as hydroxycarbamide (hydroxyurea) are used for myelosuppression, but these should be avoided in pregnancy. Anagrelide hydrochloride is an orally active quinazolinone derivative developed as a novel antiplatelet drug. There are insufficient data to recommend its use in pregnancy.
Phytochemistry of Harmal
Published in Ephraim Shmaya Lansky, Shifra Lansky, Helena Maaria Paavilainen, Harmal, 2017
Ephraim Shmaya Lansky, Shifra Lansky, Helena Maaria Paavilainen
Potential for quinazoline and quinazolinone derivatives as anticancer agents has been noted. One relevant mechanism for exerting anticancer effect of quinazolinone derivatives is on epithelial growth factor receptor (EGFR), discussed by Jafari et al. (2016) in their excellent review on the antimicrobial and cancer cytotoxic effects of the quinazoline family of compounds. EGFR is a member of a group of related proteins, the others being Her2/neu, Her3, and Her4, that are associated with upregulating cancer growth. The search for new, more effective, and safer EGFR inhibitors is a vigorous frontier of anticancer research, with a substantial part focused on quinazoline and congeners (Asadollahi-Baboli 2016; Bai et al. 2016; Hou et al. 2016; Wang Z. et al. 2015, 2016).
Prospects of Pre-clinical [6.6.0] Bicyclic Nitrogen Heterocycles in the Treatment of Tuberculosis
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Neha P. Agre, Mariam S. Degani, Sanjib Bhakta
A series of cationic fullerene derivatives bearing substituted-quinazolin-4(3H)-one moiety as side chain was evaluated by Patel et al. for their anti-TB activity against Mtb H37Rv using Lowenstein Jensen MIC method. The test tubes were incubated at 37 ± 1°C and observed at 12, 22 and 28 d to note MIC. The spheroidal fullerene when attached to the quinazolinone moiety improved the anti-TB activity. It was proposed by the authors that the quinazolinone moiety alone cannot permeate the waxy cell wall of the tubercle bacteria. The small amount of activity, i.e., 200/250 μg/mL which was observed may be due to permeation through the porin channels. The attachment of the fullerene to the molecule facilitated its permeation and potentiated its inhibitory properties. The MIC of one of the molecules decreased to 6.25 μg/mL. It was hypothesized that the introduction of a cationic charge allows the compound to better interact with the Mtb cell wall mycolic acids, leading to a decrease of the MIC of the derivatives. The most potent molecule (60) of the series with MIC of 1.562 μg/mL is depicted in Figure 7. The fullerene increased the permeability of the quinazolinone containing molecule into the cytoplasm by disrupting Mtb cell wall (Patel et al. 2013). The prospects of this molecule are highly debatable due to the presence of the C60 fullerene group, which though is reported to exhibit no acute or sub-acute toxicity in a large variety of living organisms, bacteria, fungi, leukocytes, drosophila, mice, rats and guinea pigs (Kolosnjaj et al. 2007), can still be associated with formation of reactive oxygen species that may cause inflammation and genetic damage. The beneficial or adverse effects were found to be dose-dependent (Nielsen et al. 2008). Most potent molecule (60) of the quinazolinone-fullerene series.
Design and synthesis of novel quinazolinones conjugated ibuprofen, indole acetamide, or thioacetohydrazide as selective COX-2 inhibitors: anti-inflammatory, analgesic and anticancer activities
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Asmaa Sakr, Samar Rezq, Samy M. Ibrahim, Eman Soliman, Mohamed M. Baraka, Damian G. Romero, Hend Kothayer
In continuation of our previous study, herein, we made further modifications to our previous successfully designed anti-inflammatory quinazolinones (I) (Figure 1), in order to increase their selectivity towards COX-2 inhibition13. In our current design, we kept the following: (a) the 2,3 diaryl-heterocyclic moiety (V-shape) to maintain the common structural integrity of selective COX-2 inhibitors10,11,13, (b) quinazolinone as the central heterocyclic ring due to its remarkable anti-inflammatory and analgesic activities13,14, and (c) the aryl ring at position 3 connected via an amide linker which may potentiate target interactions. Additionally, the introduction of the amide linker to the compounds allows for a bulkier structure, and thus, more favourable for COX-2 active site entry, which is approximately 20% larger than the COX-1 active site12,13.
Quinazoline and quinazolinone as important medicinal scaffolds: a comparative patent review (2011–2016)
Published in Expert Opinion on Therapeutic Patents, 2018
Abdul Hameed, Mariya Al-Rashida, Maliha Uroos, Syed Abid Ali, Marium Ishtiaq, Khalid Mohammed Khan
Quinazoline and quinazolinone are nitrogen containing heterocyclic compounds that display diverse biological activities. Quinazoline was first synthesized by Bischler and Lang in 1895. However, extensive studies on quinazoline structure was conducted by Gabriel in 1903. Depending on the varying position of nitrogen atoms, quinazoline ring has four isomeric forms, i.e. quinazoline, quinoxaline, cinnoline, and phthalazine. Quinazolinone ring is further endowed with a carbonyl group. The first quinazolinone was synthesized by P. Gries in 1869 as 2-cyanoquinazolin-4(3H)-one [1]. Different substitution pattern of carbonyl group on quinazolinone results in two isomeric forms, i.e. 2(1H)quinazolinones, and 4(3H)quinazolinones; a dicarbonyl form, 2,4(1H,3H)quinazolinedione is also known to exist (Figure 1). There are several drugs that contain quinazoline and quinazolinone ring, such as prazosin hydrochloride minipress, alfuzosin, uroxatral, bunazosin, andante, gefitinib, iressa, anagrelide agrylin/xagrid, proquazone, biarison, albaconaz code name UR-9825, linagliptin, ondero, letermovir, afatinib, gilotrif, barasertib, and dacomitinib (Figure 2) [2]. A quinazolinone-based drug raltitrexed is used for the treatment of cancer of large intestine, another drug methaqualone has sedative effects, proquazone is a non-steroidal antiinflammatory drug, and albaconazole is an antifungal drug (Figure 2) [3–6].
Design, synthesis and in vitro biological evaluation of quinazolinone derivatives as EGFR inhibitors for antitumor treatment
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Yi Le, Yiyuan Gan, Yihong Fu, Jiamin Liu, Wen Li, Xue Zou, Zhixu Zhou, Zhenchao Wang, Guiping Ouyang, Longjia Yan
Quinazolinone is a heterocyclic scaffold exhibiting a broad range of biological activities7, such as antitumor, antimicrobial, anti-inflammatory, anticonvulsant, antiviral, antidiabetic and insecticidal activities8,9. The derivatives of quinazolinone can exert anti-tumour activity by inhibiting EGFR-TK, cyclin dependent kinase 4 (CDK4)10, tubulin polymerization11, HER212, VEGFR13 and c-Met14. There are many reports of 3-position substituted quinazoline derivatives as EGFR inhibitors, such as compound I15 and II16 in Figure 2. However, the works as EGFR inhibitors of quinazoline in 2-position were few reported in literature17.