Article
Biochemistry & Molecular Biology
Vikas Kumar, Raj Kumar, Shraddha Parate, Danishuddin, Gihwan Lee, Moonhyuk Kwon, Seong-Hee Jeong, Hyeon-Su Ro, Keun Woo Lee, Seon-Won Kim
Summary: In this study, a pharmacophore model (PM) was developed based on two inhibitors and ACK1 crystal structures. The PM was used to screen a drug-like database, and the binding mode of the selected compounds was predicted through molecular docking and molecular dynamics simulations. The results showed that the hit compounds had higher binding affinity to ACK1 compared to dasatinib, a known multi-kinase inhibitor. The compounds formed desirable hydrogen bond interactions with key residues. These findings suggest that the proposed scaffolds could be used for the design of selective ACK1 inhibitors.
Article
Pharmacology & Pharmacy
Magda H. H. Abdellattif, Ahmed Elkamhawy, Mohamed Hagar, Taibi Ben Hadda, Wesam S. S. Shehab, Wael Mansy, Amany Belal, M. M. H. Arief, Mostafa A. A. Hussien
Summary: Saccharine is an active scaffold with pharmacological significance for various biological activities. In this study, saccharinyl hydrazine was synthesized and transformed into a key precursor for a series of small molecules with different moieties. The compounds exhibited strong antibacterial and anticancer activities, with 6c and 10a being the most active analogs. Theoretical calculations and molecular docking studies provided insights into the potential mechanisms of action for these compounds.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shraddha Parate, Vikas Kumar, Danishuddin, Jong Chan Hong, Keun Woo Lee
Summary: Heparanase (Hpse) is an enzyme associated with tumor growth, metastasis and angiogenesis, making it a potential target for cancer therapeutics. This study utilized a ligand-based pharmacophore model to screen a database of natural and synthetic compounds, identifying 33 potential Hpse inhibitors with better binding affinities than reference molecules. These hit compounds could serve as lead scaffolds for developing cancer treatments targeting Heparanase upregulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Physical
Vikas Kumar, Raj Kumar, Shraddha Parate, Sanghwa Yoon, Gihwan Lee, Donghwan Kim, Keun Woo Lee
Summary: In this study, a potential ACK1 inhibitor was identified using a small dataset of known inhibitors and a pharmacophore model approach. Molecular docking and dynamics simulations indicated that Hit1 and Hit2 compounds have desirable interactions with key residues of ACK1, showing promising anticancer activity.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Biochemistry & Molecular Biology
Marcelo Villagran, Carlos F. Burgos, Coralia I. Rivas, Lorena Mardones
Summary: The residues involved in the transport of dehydroascorbic acid by human GLUT1 were identified through docking studies, and functional studies further confirmed the importance of these residues in the uptake of dehydroascorbic acid and glucose analogs. The results provide structural determinants of oxidized vitamin C's transport via GLUT1 for the first time.
Article
Chemistry, Medicinal
Giulia Culletta, Mario Allegra, Anna Maria Almerico, Ignazio Restivo, Marco Tutone
Summary: Telomerase plays an important role in tumor progression and is a potential target for developing cancer therapeutics. In this study, a structure-based approach was used to design potential inhibitors of telomerase. Compound 2C showed promising activity against the K-562 cell line and demonstrated better selectivity compared to a known inhibitor. Further optimization of the structure of compound 2C is warranted to obtain more active telomerase inhibitors.
Article
Biochemistry & Molecular Biology
Avinash Kumar, Paridhi Agarwal, Ekta Rathi, Suvarna G. Kini
Summary: Human carbonic anhydrase is a type of metalloenzyme that can catalyze the hydration of carbon dioxide. Certain isoforms of this enzyme are highly expressed in the brain during seizure activity, making them potential targets for antiepileptic drugs. Through computational tools, we have identified and studied some potential inhibitors of a specific isoform of carbonic anhydrase.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Taoufik Akabli, Hamid Toufik, Fatima Lamchouri
Summary: A computational study was conducted to investigate the structural factors affecting the cytotoxic activity of a series of N9-substituted harmine derivatives. The study utilized quantitative-structure activity relationship (QSAR), pharmacophore, molecular docking, and molecular dynamics simulations to design new active derivatives. The results showed that hydrophobicity and hydrogen bonding acceptor atoms are crucial properties for cytotoxic activity. The findings were supported by the characteristics of the generated pharmacophore. The study also designed new derivatives with improved properties and demonstrated promising results in preliminary evaluations.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Benjamin R. E. Harris, Ye Zhang, Jianxin Tao, Renhui Shen, Xiaoqian Zhao, Margot P. Cleary, Tong Wang, Da-Qing Yang
Summary: Enhanced glucose uptake in cancer cells is closely correlated with poor prognosis, and the protein kinase ATM plays a key role in insulin-mediated glucose uptake. Inhibition of ATM by KU-55933 inhibits glucose uptake and glycolysis, induces apoptosis, and inhibits motility of cancer cells with overactivated Akt, showing potential as a therapeutic agent against cancer.
Article
Biochemistry & Molecular Biology
Xiaotong Chen, Yunshuo Zhao, Chuanjie He, Guanfei Gao, Jiao Li, Lu Qiu, Xiaoxi Wang, Yanfeng Gao, Yuanming Qi, Kai Sun, Jiangfeng Du
Summary: In this study, a novel GLUT1 inhibitor (SMI277) was synthesized and identified, which showed stronger inhibitory activity to glucose uptake and could inhibit cell proliferations and induce apoptosis of tumor cells. SMI277 was also able to slow down tumor growth in a mouse model and reduce tumor size.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Chemistry, Physical
Ahmed M. Abu-Dief, Nashwa M. El-Metwaly, Seraj Omar Alzahrani, Fatmah Alkhatib, Matokah M. Abualnaja, Tarek El-Dabea, Mahmoud Abd El Aleem Ali Ali El-Remaily
Summary: New pharmacologically active complexes were prepared by coordinating Pd (II), Fe (III), and Cu (II) ions with a novel ligand MPTP. The complexes were characterized through various techniques, demonstrating high stability and bioactivity, suggesting their potential as promising bioactive agents.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Chemistry, Multidisciplinary
Ya Tian, Yujie Li, Xiaojun Zheng, Qing Peng, Shuo Shen
Summary: Glucose transporter 1 (GLUT1) is highly expressed in tumor cells and plays a critical role in glucose transport. Inhibiting GLUT1 has emerged as a potential strategy for cancer treatment. This study identified potential GLUT1 inhibitors using pharmacophore-based virtual screening and evaluated their binding properties and affinity.
JOURNAL OF COMPUTATIONAL BIOPHYSICS AND CHEMISTRY
(2022)
Article
Cell Biology
Fang Wang, Qing Zhang, Hailing Zhang, Xiaogai Qiao, Xia Zhang, Ke Zhang, Xiaoli Gu, Lihong Wang, Jinquan Cui
Summary: The study found that MUC16 promotes proliferation and disease progression in EOC by regulating GLUT1 expression.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Multidisciplinary Sciences
Zhenxing Zhang, Xin Li, Fan Yang, Chao Chen, Ping Liu, Yi Ren, Pengkai Sun, Zixiong Wang, Yongping You, Yi-Xin Zeng, Xinjian Li
Summary: This study demonstrates that DHHC9-mediated GLUT1 palmitoylation at Cys207 is essential for plasma membrane localization of GLUT1 and for tumor growth in glioblastoma cells. The findings suggest a potential therapeutic target for targeting GLUT1 in cancer treatment.
NATURE COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Qun Lou, Meichen Zhang, Yanmei Yang, Yanhui Gao
Summary: Long term low dose exposure to arsenic can lead to cell proliferation and malignant transformation. In this study, it was found that low dose exposure to arsenic trioxide increased glucose uptake and promoted cell viability and DNA synthesis. The activation of AKT induced by arsenic trioxide upregulated the expression of GLUT1 on the plasma membrane, enhancing glucose uptake and cell proliferation.
Article
Biochemistry & Molecular Biology
Suliman Almahmoud, Xiaofang Wang, Jonathan L. Vennerstrom, Haizhen A. Zhong
Article
Biochemistry & Molecular Biology
Suliman Almahmoud, Haizhen A. Zhong
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Biochemistry & Molecular Biology
Suliman Almahmoud, Catherine C. Elix, Jeremy O. Jones, Corey R. Hopkins, Jonathan L. Vennerstrom, Haizhen A. Zhong
Summary: The PPAR gamma antagonist is crucial for inhibiting prostate cancer cell growth, and residues Arg288, Lys367, and His449 are important for PPAR gamma antagonist binding.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Salman A. A. Mohammed, Hussein M. Eldeeb, Hamdoon A. Mohammed, Mohsen S. Al-Omar, Suliman A. Almahmoud, Mahmoud Z. El-Readi, Ehab A. Ragab, Ghassan M. Sulaiman, Mohamed S. A. Aly, Riaz A. Khan
Summary: The study found that the aqueous-ethanolic extract, fractions, and isolated compounds of Suaeda vermiculata can effectively reduce liver damage markers in male mice, demonstrating significant hepatoprotective and antioxidant effects.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2021)
Article
Chemistry, Multidisciplinary
Sridevi Chigurupati, Fayhaa Saad Alharbi, Suliman Almahmoud, Maha Aldubayan, Yosif Almoshari, Shantini Vijayabalan, Saurabh Bhatia, Sampath Chinnam, Vijayan Venugopal
Summary: The study showed that the ethanolic extract of Olea europaea L. leaves exhibited significant antioxidant and antidiabetic properties, with high levels of phenolic compounds and flavonoids. The extract effectively scavenged free radicals and inhibited the activity of alpha-amylase, suggesting its potential as a natural bioactive source for managing diabetes and oxidative stress.
ARABIAN JOURNAL OF CHEMISTRY
(2021)
Article
Biology
Sridevi Chigurupati, Atheer Al-murikhy, Suliman A. Almahmoud, Yosif Almoshari, Amira Saber Ahmed, Shantini Vijayabalan, Shatha Ghazi Felemban, Vasanth Raj Palanimuthu
Summary: This study investigates the naturally occurring antioxidant and antidiabetic potential of Moringa oleifera ethanolic leaves extract. The results show that the Moringa oleifera extract possesses high antioxidant and antidiabetic activities.
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Plant Sciences
Seham S. El-Hawary, Rabab Mohammed, Nadia M. Lithy, Sameh Fekry AbouZid, Mostafa A. Mansour, Suliman A. Almahmoud, Bader Huwaimel, Elham Amin
Summary: Human African trypanosomiasis is a serious infectious disease that requires urgent discovery of effective drugs. In this study, 12 compounds were isolated from Euphorbia abyssinica, and 1,6-di-O-galloyl-d-glucose showed the strongest activity against trypanosomal phosphofructokinase. Molecular dynamics simulations and ADMET calculations also supported its potential as a drug candidate. Further in vitro and in vivo studies are recommended.
Article
Plant Sciences
Seham S. El-Hawary, Rabab Mohammed, Marwa A. Taher, Sameh Fekry AbouZid, Mostafa A. Mansour, Suliman A. Almahmoud, Bader Huwaimel, Elham Amin
Summary: This study isolated sixteen compounds from Tabebuia species and evaluated their anticancer activity. The results showed that three compounds (corosolic acid, luteolin-7-O-beta-glucoside, and quercetin 3-O-beta-xyloside) exhibited promising anticancer activity, suggesting their potential for further research.
Article
Plant Sciences
Ehab M. Mostafa, Hamdoon A. Mohammed, Arafa Musa, Mohamed A. Abdelgawad, Mohammad M. Al-Sanea, Suliman A. Almahmoud, Mohammed M. Ghoneim, Hesham A. M. Gomaa, Fatema El-Zahraa S. Abdel Rahman, Khaled Shalaby, Samy Selim, Riaz A. Khan
Summary: The study isolated phenanthroindolizidine alkaloids from Tylophora indica and evaluated their anticancer activity. Among the isolated compounds, tylophorinidine (5) exhibited the highest cytotoxicity against three different cancer cell lines. Molecular docking studies confirmed the bioactivity of these compounds.