Article
Biochemistry & Molecular Biology
Teymour Vahedpour, Jatinder Kaur, Salar Hemmati, Maryam Hamzeh-Mivehroud, Ali Akbar Alizadeh, Frank Wuest, Siavoush Dastmalchi
Summary: A new series of compounds for the inhibition of COX-2 were synthesized, with the lead compound showing significant COX-2 inhibition and antiproliferative activity. Molecular docking studies indicated that these compounds interact with key binding site residues of the COX-2 enzyme via multiple hydrophobic and hydrogen-bond interactions.
CHEMISTRY & BIODIVERSITY
(2021)
Article
Chemistry, Medicinal
Dalia S. El-Gamil, Ahmed K. ElHady, Po-Jen Chen, Tsong-Long Hwang, Ashraf H. Abadi, Mohammad Abdel-Halim, Matthias Engel
Summary: Clk1 kinase is a key modulator of pre-mRNA alternative splicing and could be a potential target for treating various tumors, Duchenne's muscular dystrophy, and viral infections. A new 5-methoxybenzothiophene scaffold was developed, enabling selective inhibition of Clk1 among isoenzymes. The derivatives 26a and 27a showed unprecedented selectivity and good growth inhibitory activity in cancer cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Katharigatta N. Venugopala, Mohammed Habeebuddin, Bandar E. Aldhubiab, Afzal Haq Asif
Summary: Indole-derived molecules were designed and evaluated for their anticancer activity, with 20 candidate molecules showing promising anti-proliferative effects. Compounds with hydroxy phenyl substitution on the pyrazoline ring demonstrated potent activity across all tested cell lines, indicating potential for further optimization as anticancer agents.
Article
Chemistry, Medicinal
Zoltan Orgovan, Nikolett Peczka, Laszlo Petri, Peter Abranyi-Balogh, Ivan Randelovic, Szilard Toth, Gergely Szakacs, Kinga Nyiri, Beata Vertessy, Gyula Palfy, Istvan Vida, Andras Perczel, Jozsef Tovari, Gyorgy M. Keseru
Summary: Covalent fragment screening of a diverse library of non-covalent scaffolds equipped with 40 different electrophilic functionalities identified two potential inhibitor chemotypes targeting the G12C mutant KRas. These scaffolds showed promising results in in vitro cellular and in vivo xenograft models, demonstrating their potential as starting points for covalent drug discovery programs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Medicine, Research & Experimental
Alberto Fernando Oliveira Justo, Eliana Cristina de Brito Toscano, Daniela Souza Farias-Itao, Claudia Kimie Suemoto
Summary: Alzheimer's disease (AD) is the leading cause of dementia worldwide, and the deposition of beta-amyloid in the brain is partially responsible for its etiology. Despite extensive research, current treatments for AD are ineffective. This study systematically reviewed the use of phosphodiesterase 5 inhibitors (PDE5i) in rodent models with beta-amyloid accumulation and found that PDE5i was efficient in reducing beta-amyloid levels in the hippocampi and preventing cognitive decline. However, further experimental studies are needed to evaluate the molecular mechanisms of PDE5i in beta-amyloid removal in both male and female animals.
Article
Chemistry, Organic
Gao Chao, Zhang Yutong, Chi Lingling, Wang Hao, Ma Jiajie, Bi Mengxin, Dai Honglin, Si Xiaojie, Liu Limin, Zhang Yang, Zheng Jiaxin, Ke Yu, Liu Hongmin, Zhang Qiurong
Summary: A series of 2,4,6-trisubstituted pyrimidine derivatives were synthesized and evaluated for their antiproliferative activities against human tumor cell lines. The results showed that these compounds exhibited moderate to potent antiproliferative activities. In particular, compound 19q had the best inhibitory activity against prostate cancer cells and could induce apoptosis. It may exert its antitumor effect by regulating the expression of apoptosis-related proteins.
CHINESE JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Jagadeesha Gullahalli Swathantraiah, Sudhanva Muddenahalli Srinivasa, Anil Kumar Belagal Motatis, Akshay Uttarkar, Shwetha Bettaswamygowda, Sridhar Bilgumba Thimmaiah, Vidya Niranjan, Shobith Rangappa, Rangappa Kanchugarakoppal Subbegowda, Thimmegowda Naraganahalli Ramegowda
Summary: Synthetic small molecules effectively target overexpressed oncogenic proteins to induce apoptosis in cancer cells, showing potential for cancer treatment.
Article
Cell Biology
Rakesh C. Kukreja, Rui Wang, Saisudha Koka, Anindita Das, Arun Samidurai, Lei Xi
Summary: This article discusses the potential use of combination therapy with PDE5 inhibitor and HCQ in the treatment of type 2 diabetes (T2D). Previous studies have shown that this combination treatment can reduce blood glucose and lipid levels, improve insulin sensitivity, and reduce myocardial infarction.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Review
Cardiac & Cardiovascular Systems
Aaron Gopal, Tarun Sharma, Joe B. Calkins
Summary: Erectile dysfunction is common and can be treated with phosphodiesterase inhibitors, but caution is needed in patients with cardiovascular issues. The safety of using PDE5 inhibitors in patients with valvular heart disease requires further research.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
(2021)
Review
Chemistry, Medicinal
Ahmed K. Elhady, Dalia S. El-Gamil, Mohammad Abdel-Halim, Ashraf H. Abadi
Summary: This review provides an updated assessment of the crucial role played by phosphodiesterase 5 (PDE5) inhibitors in the nitric oxide/cGMP pathway and their potential in treating various diseases. It discusses the medicinal chemistry and drug discovery aspects of PDE5 inhibitors, as well as the breakthrough development of allosteric inhibitors. Furthermore, the concept of multi-targeted ligands in relation to PDE5 inhibitors is critically evaluated.
Article
Rehabilitation
Tri Pham, Adam Butler, Rick A. Weideman, Thiru M. Annaswamy
Summary: This study explores the association between phosphodiesterase 5 inhibitor use and the prevalence of lumbar decompression surgery in patients with lumbar spinal stenosis. The results suggest that patients on phosphodiesterase 5 inhibitor therapy have a significantly lower surgical rate for lumbar decompression surgery compared to the control group.
AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
(2022)
Article
Biochemistry & Molecular Biology
Roberta Listro, Alessio Malacrida, Francesca Alessandra Ambrosio, Giacomo Rossino, Marcello Di Giacomo, Valeria Cavalloro, Martina Garbagnoli, Pasquale Linciano, Daniela Rossi, Guido Cavaletti, Giosue Costa, Stefano Alcaro, Mariarosaria Miloso, Simona Collina
Summary: The research team isolated a secondary metabolite called Hib-ester from Hibiscus Sabdariffa L. calyces, which possesses antiproliferative properties against human MM. Compound 13 and 14 were found to be more potent than Hib-ester, providing a new chemical class for developing possible drug candidates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Obstetrics & Gynecology
Carolyn E. Cesta, Silvia Segovia Chacon, Anders Engeland, Anne Broe, Per Damkier, Kari Furu, Helle Kieler, Par Karlsson
Summary: In the Scandinavian countries over the last decades, few pregnant women used PDE5 inhibitors, with only a small proportion having a diagnosis of pulmonary arterial hypertension, suggesting off-label use in most cases. The majority of users were mothers over the age of 35. The safety of fetal exposure to sildenafil and other PDE5 inhibitors during pregnancy has not been established and further evaluation is needed as maternal age increases and additional uses are explored.
ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA
(2021)
Article
Biochemistry & Molecular Biology
Dmitry I. Ivankin, Tatyana E. Kornienko, Marina A. Mikhailova, Nadezhda S. Dyrkheeva, Alexandra L. Zakharenko, Chigozie Achara, Johannes Reynisson, Victor M. Golyshev, Olga A. Luzina, Konstantin P. Volcho, Nariman F. Salakhutdinov, Olga I. Lavrik
Summary: A novel series of 3,5-disubstituted thiazolidine-2,4-diones were synthesized and tested for their activity against TDP1. Compounds 20d and 21d showed the highest activity with IC50 values in the submicromolar range. However, these compounds did not exhibit cytotoxicity against HCT-116 (colon carcinoma) and MRC-5 (human lung fibroblasts) cell lines in the concentration range of 1-100 μM, and they also did not sensitize cancer cells to the cytotoxic effect of topotecan.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Aiste-Monika Jakstaite, Peter Luedike, Bastian Schmack, Nikolaus Pizanis, Matthias Riebisch, Alexander Weymann, Markus Kamler, Arjang Ruhparwar, Tienush Rassaf, Maria Papathanasiou
Summary: Long-term use of PDE5Is after LVAD implantation is associated with increased overall bleeding risk, although differences were not significant in major bleeding and gastrointestinal bleeding.
Article
Chemistry, Medicinal
Yasmeen T. AlNajjar, Moustafa Gabr, Ahmed K. ElHady, Mohamed Salah, Gerrit Wilms, Ashraf H. Abadi, Walter Becker, Mohammad Abdel-Halim, Matthias Engel
Summary: The study found that dual inhibitors with higher selectivity for Dyrk1A and inhibition of alpha-synuclein aggregation present a potential novel therapeutic strategy for Parkinson's disease. Compound b27, displaying the highest inhibitory potency and selectivity, could be a promising drug candidate for PD treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Analytical
Hani M. Hafez, Mohammad Abdel-Halim, Ahmed Hemdan, Mennatallah A. Hammam
Summary: A new method for accurately quantifying baloxavir marboxil and its degradation products was developed, and the degradation kinetics of baloxavir marboxil under different stress conditions were revealed. The structural characterization of baloxavir marboxil degradation products was also performed.
JOURNAL OF SEPARATION SCIENCE
(2022)
Review
Chemistry, Medicinal
Ahmed K. ElHady, Dalia S. El-Gamil, Ashraf H. Abadi, Mohammad Abdel-Halim, Matthias Engel
Summary: Clk1 has been identified as a promising target for the treatment of various diseases, especially those related to deregulated alternative splicing. Clinical trials of small molecule inhibitors targeting Clk1 are underway for the treatment of solid cancer, which is promoted by oncogenic protein variants derived from alternative splicing. In addition, Clk1 has been implicated in the progression of Alzheimer's disease. However, most Clk1 inhibitors lack sufficient selectivity, affecting other Clk isoforms and Dyrk kinases.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Pharmacology & Pharmacy
Amr Hefnawy, Matthew J. Herpin, Michael Easton, Shrinidh Joshi, Don Jordan, Hugh D. C. Smyth, Jonathan Tarpy
Summary: This article reports the development and optimization of the ARI(TM) smart pMDI inhaler device with integrated spacer functionality. The design was optimized using simulations and validated through in vitro experiments. The results show that the ARI(TM) device, with its converging-diverging nozzle design, improves airflow and enhances the mixing between inhalation air and the propellent jet, leading to better aerosol performance compared to the unmodified Symbicort inhaler and the OptiChamber spacer.
JOURNAL OF PHARMACEUTICAL INNOVATION
(2023)
Article
Chemistry, Medicinal
Dalia S. El-Gamil, Ahmed K. ElHady, Po-Jen Chen, Tsong-Long Hwang, Ashraf H. Abadi, Mohammad Abdel-Halim, Matthias Engel
Summary: Clk1 kinase is a key modulator of pre-mRNA alternative splicing and could be a potential target for treating various tumors, Duchenne's muscular dystrophy, and viral infections. A new 5-methoxybenzothiophene scaffold was developed, enabling selective inhibition of Clk1 among isoenzymes. The derivatives 26a and 27a showed unprecedented selectivity and good growth inhibitory activity in cancer cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Moustafa M. Abdelaziz, Amr Hefnawy, Asem Anter, Menna M. Abdellatif, Mahmoud A. F. Khalil, Islam A. Khalil
Summary: The pulmonary route of administration is a promising method for treating lung infections. This study presents the design of an inhalable dry-powder formulation composed of vancomycin-conjugated iron oxide magnetic nanoparticles core and a lactose microparticle shell. The formulated lactose microparticles showed desirable physical and chemical properties, allowing the vancomycin-conjugated nanoparticles to reach the infection site in the lung tissues.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Lina Ammar, Hung-Yu Lin, Shou-Ping Shih, Tsen-Ni Tsai, Yu-Ting Syu, Mohammad Abdel-Halim, Tsong-Long Hwang, Ashraf H. Abadi
Summary: PDE5 inhibitors have anticancer effects and cGMP elevation plays a role in CRC. We synthesized 31 derivatives of 9-benzylaminoacridine and found 22 of them showed micromolar or sub-micromolar inhibition against PDE5. Compounds 11, 12, and 28 exhibited significant growth inhibition, superior Topo II inhibitory activity, low micromolar PDE5 inhibition, and affected cell cycle progression in HCT-116 CRC cells. These compounds have potential as effective therapeutic agents against cancer.
Article
Oncology
Heather N. Tinsley, Bini Mathew, Xi Chen, Yulia Y. Maxuitenko, Nan Li, Whitney M. Lowe, Jason D. Whitt, Wei Zhang, Bernard D. Gary, Adam B. Keeton, William E. Grizzle, Clinton J. Grubbs, Robert C. Reynolds, Gary A. Piazza
Summary: This study introduces a new compound, sulindac sulfide amide (SSA), which is derived from the nonsteroidal anti-inflammatory drug (NSAID) sulindac. SSA eliminates the side effects associated with long-term NSAID use while remaining more potent in inhibiting growth and inducing apoptosis of breast cancer cells. Its anti-cancer activity is associated with the inhibition of cGMP PDE enzymes.
Article
Chemistry, Medicinal
Youssef Y. Helmi, Niklas Papenkordt, Georg Rennar, Florence Gbahou, Ahmed K. El-Hady, Nedjma Labani, Karin Schmidtkunz, Stefan Boettcher, Ralf Jockers, Mohammad Abdel-Halim, Manfred Jung, Darius P. Zlotos
Summary: Anticancer drug conjugates that merge melatonin with the HDAC inhibitor vorinostat have shown higher potency in inhibiting HDAC and suppressing cancer cell growth. The most effective inhibitors, 3e, 5c, and 7c, linked the hydroxamic acid group of vorinostat to melatonin through a hexamethylene spacer. These hybrid ligands also demonstrated strong growth inhibition on various cancer cell lines. Their anticancer actions are driven by HDAC inhibition rather than melatonin receptor activation.
ARCHIV DER PHARMAZIE
(2023)
Article
Biochemistry & Molecular Biology
Donia E. Hafez, Mariam Dubiel, Gabriella La Spada, Marco Catto, David Reiner-Link, Yu-Ting Syu, Mohammad Abdel-Halim, Tsong-Long Hwang, Holger Stark, Ashraf H. Abadi
Summary: Introduced a multi-targeted ligand for neurodegenerative diseases, such as Alzheimer's disease, which offers an improved therapeutic alternative compared to the traditional one-target, one-molecule approach. Certain compounds showed potential for multi-targeting by evaluating their interactions with AChE, BuChE, and MAO-B, suggesting their potential as lead structures for developing new multi-targeting anti-AD agents.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Reem K. Fathalla, Matthias Engel, Christian Ducho
Summary: 8-Anilinonaphthalene-1-sulfonic acid (ANS) is a fluorescent probe commonly used to detect conformational changes in proteins. This study discovered that ANS can inhibit the activity of various isoforms of MurA and identified a more potent ANS analog. These findings highlight the potential of targeting the ANS binding pocket for the development of antibiotics.
ARCHIV DER PHARMAZIE
(2023)
Review
Chemistry, Medicinal
Ahmed K. Elhady, Dalia S. El-Gamil, Mohammad Abdel-Halim, Ashraf H. Abadi
Summary: This review provides an updated assessment of the crucial role played by phosphodiesterase 5 (PDE5) inhibitors in the nitric oxide/cGMP pathway and their potential in treating various diseases. It discusses the medicinal chemistry and drug discovery aspects of PDE5 inhibitors, as well as the breakthrough development of allosteric inhibitors. Furthermore, the concept of multi-targeted ligands in relation to PDE5 inhibitors is critically evaluated.
Article
Chemistry, Medicinal
Reem A. Wagdy, Nader S. Abutaleb, Reem K. Fathalla, Yehia Elgammal, Stefanie Weck, Rusha Pal, Patrick D. Fischer, Christian Ducho, Ashraf H. Abadi, Mohamed N. Seleem, Matthias Engel, Mohammad Abdel-Halim
Summary: The synthesis of novel compounds targeting the cytoplasmic steps of peptidoglycan synthesis as potential antibacterial agents was reported. Some of these compounds showed potent inhibition of MurA enzyme and exhibited antibacterial activity against Clostridioides difficile strains. The inhibition of MurA enzyme was found to be responsible for the observed effect on bacterial growth.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)