4.7 Review

Thieno[2,3-d] pyrimidine as a promising scaffold in medicinal chemistry: Recent advances

期刊

BIOORGANIC & MEDICINAL CHEMISTRY
卷 27, 期 7, 页码 1159-1194

出版社

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2019.02.044

关键词

Thienopyrimidine; Anti-inflammatory; Anticancer; Antimicrobial; Antiviral; CNS protective agents

资金

  1. Korea Institute of Science and Technology (KIST) [2E27930]

向作者/读者索取更多资源

Thienopyrimidine scaffold is a fused heterocyclic ring system that structurally can be considered as adenine, the purine base that is found in both DNA and RNA-bioisosteres. Thienopyrimidines exist in three distinct isomeric forms. The current review discusses thieno[2,3-d] pyrimidine as a one of the opulent heterocycles in drug discovery. Its broad range of medical applications such as anticancer, anti-inflammatory, anti-microbial, and CNS protective agents has inspired us to study its structure-activity relationship (SAR), along with its relevant synthetic strategies. The present review briefly summarizes synthetic approaches for the preparation of thieno[2,3-d] pyrimidine derivatives. In addition, the promising biological activities of this scaffold are also illustrated with explanatory diagrams for their SAR studies.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Biochemistry & Molecular Biology

Design, synthesis and anti-inflammatory activity of imidazol-5-yl pyridine derivatives as p38α/MAPK14 inhibitor

Eslam M. H. Ali, Mohammed S. Abdel-Maksoud, Rasha Mohamed Hassan, Karim I. Mersal, Usama M. Ammar, Choi Se-In, Han He-Soo, Hee-Kwon Kim, Anna Lee, Kyung-Tae Lee, Chang-Hyun Oh

Summary: In this study, drug repurposing strategies were used to reposition a series of inhibitors to target P38α kinase, leading to the identification of compounds with anti-inflammatory activity by effectively inhibiting the production of inflammatory cytokines. The most potent inhibitor, compound 11d, exhibited satisfactory inhibitory activity against the production of PGE2 and NO in LPS-stimulated macrophages.

BIOORGANIC & MEDICINAL CHEMISTRY (2021)

Article Chemistry, Medicinal

Design, synthesis, biological evaluation, and docking studies of novel (imidazol-5-yl)pyrimidine-based derivatives as dual BRAFV600E/p38α inhibitors

Eslam M. H. Ali, Rania Farag A. El-Telbany, Mohammed S. Abdel-Maksoud, Usama M. Ammar, Karim Mersal, Seyed-Omar Zaraei, Mohammed El-Gamal, Se-In Choi, Kyung-Tae Lee, Hee-Kwon Kim, Kwan Hyi Lee, Chang-Hyun Oh

Summary: The newly synthesized (imidazol-5-yl)pyrimidine compounds exhibited dual inhibitory activity against BRAF(V600E) and p38 alpha kinases, as well as antiproliferative and TNF-alpha inhibitory activities. Compound 20h showed the highest inhibitory activity among the tested compounds.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Chemistry, Medicinal

Discovery of New Imidazo[2,1-b]thiazole Derivatives as Potent Pan-RAF Inhibitors with Promising In Vitro and In Vivo Anti-melanoma Activity

Mohammed S. Abdel-Maksoud, Mohammed El-Gamal, Bong S. Lee, Mahmoud M. Gamal El-Din, Hong R. Jeon, Dow Kwon, Usama M. Ammar, Karim Mersal, Eslam M. H. Ali, Kyung-Tae Lee, Kyung Ho Yoo, Dong Keun Han, Jae Kyun Lee, Garam Kim, Hong Seok Choi, Young Jik Kwon, Kwan Hyi Lee, Chang Hyun Oh

Summary: In this study, a series of new (imidazo[2,1-b]thiazol-5-yl)pyrimidine derivatives with a terminal sulfonamide moiety were synthesized and their pan-RAF inhibitory effect was investigated. Compounds 27c and 38a showed the highest antiproliferative activity against cancer cells and were able to inhibit phosphorylation of MEK and ERK. Compound 38a was further tested for its in vivo activity against melanoma, and both cellular and animal activities were reported.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Chemistry, Medicinal

Design, synthesis, in vitro determination and molecular docking studies of 4-(1-(tert-butyl)-3-phenyl-1H-pyrazol-4-yl) pyridine derivatives with terminal sulfonamide derivatives in LPS-induced RAW264.7 macrophage cells

Karim I. Mersal, Mohammed S. Abdel-Maksoud, Eslam M. H. Ali, Usama M. Ammar, Seyed-Omar Zaraei, Jae-Min Kim, Su-Yeon Kim, Kyung-Tae Lee, Kwan Hyi Lee, Si-Won Kim, Hyun-Mee Park, Mi-Jung Ji, Chang-Hyun Oh

Summary: In this study, a new series of compounds were designed and synthesized with potential cytotoxic and anti-inflammatory effects. Compounds 8d and 9k showed the highest inhibitory effect on NO production, PGE(2) inhibition, and cytokines inhibition. Additionally, compounds 8d and 9k exhibited high binding affinity to the COX-2 active site, similar to the native ligand celecoxib.

MEDICINAL CHEMISTRY RESEARCH (2021)

Article Chemistry, Medicinal

Design and synthesis of novel quinazolinone-based fibrates as PPARα agonists with antihyperlipidemic activity

Rasha M. Hassan, Islam H. Ali, Mohammed S. Abdel-Maksoud, Heba M. I. Abdallah, Ahmed M. El Kerdawy, Francesca Sciandra, Iman A. Y. Ghannam

Summary: Compound 9q demonstrated potent antihyperlipidemic and antioxidant activities, lowering blood lipid levels and enhancing antioxidant capacity, with improvements in aortic architecture and hepatic steatosis.

ARCHIV DER PHARMAZIE (2022)

Article Biochemistry & Molecular Biology

Anticancer profile and anti-inflammatory effect of new N-(2-((4-(1,3-diphenyl-1H-pyrazol-4-yl)pyridine sulfonamide derivatives

Mohammed S. Abdel-Maksoud, Rasha Mohamed Hassan, Aida Abdel-Sattar El-Azzouny, Mohamed Nabil Aboul-Enein, Chang-Hyun Oh

Summary: In this study, a novel series of anticancer and anti-inflammatory compounds were designed and synthesized, with compound 11c showing the highest anticancer activity and compound 11n demonstrating the most potent anti-inflammatory effects. These compounds were further analyzed for their biological targets and structure-activity relationships, indicating potential clinical applications.

BIOORGANIC CHEMISTRY (2021)

Article Chemistry, Medicinal

Discovery of first-in-class imidazothiazole-based potent and selective ErbB4 (HER4) kinase inhibitors

Seyed-Omar Zaraei, Rawan M. Sbenati, Nour N. Alach, Hanan S. Anbar, Randa El-Gamal, Hamadeh Tarazi, Mahmoud K. Shehata, Mohammed S. Abdel-Maksoud, Chang-Hyun Oh, Mohammed El-Gamal

Summary: This article reports on novel imidazothiazole derivatives as first-in-class potent and selective ErbB4 (HER4) inhibitors. The compounds showed promising antiproliferative activity with high selectivity towards cancer cell lines, indicating potential therapeutic value.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Biochemistry & Molecular Biology

Design, Synthesis and Anticancer Profile of New 4-(1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine-Linked Sulfonamide Derivatives with V600EBRAF Inhibitory Effect

Mohammed S. Abdel-Maksoud, Ahmed A. B. Mohamed, Rasha M. Hassan, Mohamed A. Abdelgawad, Garri Chilingaryan, Samy Selim, Mohamed S. Abdel-Bakky, Mohammad M. Al-Sanea

Summary: A new series of 4-(1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine linked sulfonamide derivatives were designed and synthesized based on established V600EBRAF inhibitors. Among them, 12e, 12i, and 12l showed the strongest inhibitory activity against V600EBRAF, with 12l having the lowest IC50 of 0.49 μM. Further studies revealed that 12e exhibited significant growth inhibition against multiple cancer cell lines and warrants further investigation into its effect on cell cycle progression. Additionally, virtual docking studies provided insights into the binding modes of vemurafenib and the synthesized compounds.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Article Pharmacology & Pharmacy

Structural optimization of 4-(imidazol-5-yl)pyridine derivatives affords broad-spectrum anticancer agents with selective B-RAFV600E/p38a kinase inhibitory activity: Synthesis, in vitro assays and in silico study

Eslam M. H. Ali, Karim Mersal, Usama M. Ammar, Seyed-Omar Zaraei, Mohammed S. Abdel-Maksoud, Mohammed El-Gamal, Md Mamunul Haque, Tanuza Das, Eunice EunKyeong Kim, Jun-Seok Lee, Kwan Hyi Lee, Hee-Kwon Kim, Chang-Hyun Oh

Summary: In this article, a new series of 4-(imidazol-5-yl)pyridines with improved anticancer activity and selective B-RAF(V600E)/p38 alpha kinase inhibitory activity was designed and evaluated. Compound 10c exhibited the highest potency among the tested compounds, with nano-molar activity against most cancer cell lines and incredible activity against melanoma. It also induced cell cycle arrest, apoptosis, and autophagy in multiple cancer cell lines.

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES (2022)

Article Infectious Diseases

Imidazothiazole Derivatives Exhibited Potent Effects against Brain-Eating Amoebae

Ruqaiyyah Siddiqui, Mohammed El-Gamal, Anania Boghossian, Balsam Qubais Saeed, Chang-Hyun Oh, Mohammed S. Abdel-Maksoud, Ahmad M. Alharbi, Hasan Alfahemi, Naveed Ahmed Khan

Summary: The synthesized compounds exhibited significant anti-amoebic effects against brain-eating amoebae, showing promise as effective treatments for these infections.

ANTIBIOTICS-BASEL (2022)

Article Infectious Diseases

Antiamoebic Activity of Imidazothiazole Derivatives against Opportunistic Pathogen Acanthamoeba castellanii

Noor Akbar, Mohammed El-Gamal, Balsam Qubais Saeed, Chang-Hyun Oh, Mohammed S. Abdel-Maksoud, Naveed Ahmed Khan, Ahmad M. Alharbi, Hasan Alfahemi, Ruqaiyyah Siddiqui

Summary: This study found that compounds 1m and 1zb exhibited excellent anti-amoebic effects against Acanthamoeba. These compounds significantly inhibited the proliferation of Acanthamoeba trophozoites and blocked the encystation and excystation processes. They also showed minimal cytotoxic effects on host cells and reduced amoeba-mediated host cell death.

ANTIBIOTICS-BASEL (2022)

Article Chemistry, Medicinal

Design and synthesis of new adamantyl derivatives as promising antiproliferative agents

Afnan Shahin, Seyed-Omar Zaraei, Bilal O. AlKubaisi, Saif Ullah, Hanan S. Anbar, Randa El-Gamal, Varsha Menon, Mohammed S. Abdel-Maksoud, Chang-Hyun Oh, Raafat El-Awady, Nicolly Espindola Gelsleichter, Julie Pelletier, Jean Sevigny, Jamshed Iqbal, Taleb H. Al-Tel, Mohammed El-Gamal

Summary: A series of adamantyl carboxamide derivatives containing sulfonate or sulfonamide moiety were designed and evaluated for their antiproliferative activity against NCI-60 cancer cell lines panel. Compounds 1e and 1i exhibited potent and broad-spectrum inhibition against multiple cancer subtypes while showing safety towards normal cells.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2023)

Article Biochemistry & Molecular Biology

Design and synthesis of novel rigid dibenzo[b,f]azepines through ring closure technique as promising anticancer candidates against leukaemia and acting as selective topoisomerase II inhibitors and DNA intercalators

Mohammed Farrag El-Behairy, Walaa Hamada Abd-Allah, Mohamed M. M. Khalifa, Mohamed S. S. Nafie, Mohamed A. A. Saleh, Mohammed S. S. Abdel-Maksoud, Tarfah Al-Warhi, Wagdy M. M. Eldehna, Ahmed A. A. Al-Karmalawy

Summary: Based on the rigidification principle and doxorubicin's pharmacophoric features, two novel series of dibenzo[b,f]azepines (14 candidates) were designed and synthesised. The anti-proliferative activity and topoisomerase II inhibition ability of the promising candidates (5a-g) were evaluated, with 5e identified as the most active congener. Moreover, 5e exhibited cytotoxicity against leukaemia SR cells, arrested the cell cycle at the G1 phase, increased apoptosis ratio, and showed inhibition of tumor proliferation and volume decrease in in vivo studies.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2023)

Review Biochemistry & Molecular Biology

New horizons in drug discovery of lymphocyte-specific protein tyrosine kinase (Lck) inhibitors: a decade review (2011-2021) focussing on structure-activity relationship (SAR) and docking insights

Ahmed Elkamhawy, Eslam M. H. Ali, Kyeong Lee

Summary: Lymphocyte-specific protein tyrosine kinase (Lck), a non-receptor Src family kinase, plays a crucial role in regulating cellular processes and T-cell functions. Alterations in Lck expression and activity can lead to various diseases, prompting research efforts to develop new Lck inhibitors and explore their binding modes within the active site of Lck for potential therapeutic applications.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2021)

暂无数据