Article
Biochemistry & Molecular Biology
Mersedeh Shayan, Soghra Mehri, Bibi Marjan Razavi, Hossein Hosseinzadeh
Summary: This study demonstrates that minocycline can protect cells against cadmium-induced oxidative stress and apoptotic cell death, and exhibits antioxidant and anti-apoptotic activity.
BIOLOGICAL TRACE ELEMENT RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Mersedeh Shayan, Soghra Mehri, Bibi Marjan Razavi, Hossein Hosseinzadeh
Summary: Arsenic is a naturally occurring metalloid that can cause acute and chronic toxicity in humans. Neurotoxicity is a serious manifestation of arsenic toxicity. This study found that minocycline, an antimicrobial agent with antioxidant properties and the ability to cross the blood-brain barrier, can significantly attenuate arsenic-induced neurotoxicity by reducing oxidative stress and apoptosis. These findings suggest that minocycline could be a promising treatment for arsenic toxicity.
BIOLOGICAL TRACE ELEMENT RESEARCH
(2023)
Article
Medicine, Research & Experimental
Shanshan Qiao, Dexin Yang, Xiaofeng Li, Weiping Li, Yuan Zhang, Wenlan Liu
Summary: The study reveals the crucial role of PAQR3 in ischemia/reperfusion injury, showing that silencing PAQR3 protects neuronal cells and improves cell survival by inhibiting the apoptosis pathway. Knockdown of PAQR3 significantly attenuates apoptosis and increases cell viability, offering a novel therapeutic target for preventing cerebral ischemia/reperfusion injury.
Article
Multidisciplinary Sciences
PinFen Chua, William K. Lim
Summary: This study investigated the applications of different PC12 variants in neuroprotection research, identifying optimal culture conditions for PC12 Riken and NS-1 cells, and determining collagen IV as the preferred adhesive substrate for both cell lines. In the in vitro stroke model, NS-1 cells achieved a maximal differentiation of 72.7% after optimization, and the 5-HT1A agonist 8-OH-DPAT was found to be neuroprotective in PC12 cells.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Jonathan Gagnon, Veronique Caron, Laurent Gyenizse, Andre Tremblay
Summary: This study uncovers a non-canonical SUMOylation mechanism of Nor1, which detrimentally affects gene transcription and oxidative stress response, leading to impaired neuronal cell growth and survival ability.
Article
Pharmacology & Pharmacy
Fatemeh Forouzanfar, Elham Asadpour, Hossein Hosseinzadeh, Mohammad Taher Boroushaki, Afrouz Adab, Seyedeh Hoda Dastpeiman, Hamid R. Sadeghnia
Summary: Safranal, isolated from saffron, has been shown to possess neuroprotective effects. This study demonstrated that safranal can attenuate ischemia/reperfusion-induced PC12 cell injury by modulating oxidative and apoptotic responses, thereby protecting against neurotoxicity.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2021)
Article
Infectious Diseases
Oskar Ekelund, Marit Andrea Klokkhammer Hetland, Iren Hoyland Lohr, Thomas Schon, Sofia Somajo
Summary: A rapid and sensitive flow cytometry-based colistin resistance testing method for E. coli and K. pneumoniae was developed and shown to have higher efficiency and accuracy compared to the traditional BMD method.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Neurosciences
Ayesha Singh, Oliver Chow, Stuart Jenkins, Lingling Zhu, Emily Rose, Katherine Astbury, Ruoli Chen
Summary: Preconditioning tissue with sublethal ischaemia or hypoxia can confer tolerance against subsequent ischaemic challenge. In vitro ischaemic preconditioning is typically achieved through oxygen glucose deprivation (OGD), whereas hypoxic preconditioning involves oxygen deprivation alone. The study found that preconditioning with reduced glucose or OGD for 4 hours before reperfusion and ischaemic challenge led to enhanced mitochondrial activity, reduced cytotoxicity, and decreased apoptosis compared to sham preconditioned cells. Additionally, preconditioning with reduced glucose concentration conferred protective effects, while preconditioning with higher concentrations did not.
Article
Environmental Sciences
Kaniz Fatima Binte Hossain, Md Mostafizur Rahman, Md Tajuddin Sikder, Toshiyuki Hosokawa, Takeshi Saito, Masaaki Kurasaki
Summary: This study investigated the protective role of selenium (Se) against inorganic mercury (iHg) toxicity in PC12 cells. Results showed that Se co-treatment inhibited intrinsic apoptosis and oxidative stress induced by iHg through various mechanisms, suggesting that excessive ROS generation plays a critical role in iHg-induced oxidative stress and Se has potential in attenuating iHg cytotoxicity via its antioxidant properties.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Plant Sciences
Wenjing Ding, Chen Chen, Jun Li, Xuexia Geng, Haijun Zhang, Yuxuan Sun
Summary: QA root extract inhibits cell proliferation and migration in breast cancer cells and induces changes in cell morphology, while regulating mitochondria-mediated apoptotic and autophagic cell death processes.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Edumpan Jaisankar, Raja Sulaiman Azarudeen, Marimuthu Thirumarimurugan
Summary: This study successfully fabricated drug loaded nanofiber mats, which attracted clinicians for its profound cancer therapy and growth controlling effect towards microbial infections. The nanofiber mats, decorated with nanoscale silver oxide (<10 nm) and loaded with anticancer drug, exhibited controlled drug release for two weeks. The mats effectively eradicated breast cancer cell line in 24 h with a release of similar to 15% drug and showed profound cell viability against fibroblast cell line. In addition, the mats strongly inhibited post-surgical microbial infections. The fabricated nanofiber mats have great potential for drug delivery and tissue engineering implants.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chintha Venkataramaiah, Bandila Lakshmi Priya, Sholapuri Payani, Jangampalli Adi Pradeepkiran
Summary: The study investigated the pharmacological effect and therapeutic mechanism of a natural plant compound against ketamine-induced toxicity in PC 12 cell lines. Results showed that the compound significantly increased cell viability, reduced cell damage, decreased free radical damage, and enhanced cell survival capacity.
Article
Chemistry, Multidisciplinary
Klaudia Glowacz, Sandra Skorupska, Ilona Grabowska-Jadach, Patrycja Ciosek-Skibinska
Summary: Monitoring cells viability is crucial in biomedical applications, and spectroscopic techniques offer non-invasive, label-free, and non-destructive advantages. This study demonstrates that excitation-emission matrix fluorescence spectroscopy can reliably determine cells viability with high correlation to the MTT test.
Article
Pharmacology & Pharmacy
Yihui Song, Min Zhao, Yahong Wu, Bin Yu, Hong-Min Liu
Summary: A high-throughput screening protocol was developed to discover SHP2 inhibitors, resulting in the identification of new SHP2-PTP inhibitors and allosteric inhibitors. These inhibitors showed potential for targeting cancer-associated SHP2 mutations.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Reproductive Biology
Jing Pang, Hua Yang, Xu Feng, Qi Wang, Yu Cai, Zifei Liu, Changjian Wang, Feng Wang, Yanli Zhang
Summary: HT-2 toxin exerts toxic effects on goat spermatogonial stem cells, leading to decreased cell viability and proliferation, disruption of self-renewal ability, and induction of cell apoptosis and oxidative stress. Additionally, HT-2 toxin exposure also induces autophagy in goat SSCs, possibly through the AMPK-mTOR-ULK1 pathway.
Article
Chemistry, Medicinal
Shikha Kumari, Angelica Carmona, Amit K. Tiwari, Paul C. Trippier
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Review
Oncology
Sachin Sharma, Arshdeep Singh, Sahil Sharma, Ram Sharma, Jagjeet Singh, Nihar Kinarivala, Kunal Nepali, Jing P. Liou
Summary: Quinoline, a privileged heterocyclic ring, has shown substantial antiproliferative effects through diverse mechanisms of actions in anticancer compounds. Its flexibility and accessibility to structural changes make it a promising option for chemically distinct anti-tumor constructs.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Bader I. Huwaimel, Myla Bhakta, Chaitanya A. Kulkarni, Alexander S. Milliken, Feifei Wang, Aimin Peng, Paul S. Brookes, Paul C. Trippier
Summary: Study investigated benzothiadiazine derivatives for CII inhibition and their impact on cancer cells, identifying compounds with greater antineoplastic effect in triple-negative breast cancer cells compared to clinical agents. No correlation found between cytotoxicity and CII inhibition, suggesting undefined mechanism of action for this scaffold.
Article
Chemistry, Medicinal
Md Shafikur Rahman, Shikha Kumari, Shiva Hadi Esfahani, Saeideh Nozohouri, Srinidhi Jayaraman, Nihar Kinarivala, Joanna Kocot, Andrew Baez, Delaney Farris, Thomas J. Abbruscato, Vardan T. Karamyan, Paul C. Trippier
Summary: Upregulation of Nln has been identified as a critical endogenous cerebroprotective mechanism after stroke, making it a potential target for the treatment of ischemic stroke. Discovery and optimization of first-in-class Nln activators based on histidine-containing dipeptide hits have led to compounds with improved brain penetration, stability, and potency for drug discovery efforts.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Correction
Chemistry, Medicinal
Md. Shafikur Rahman, Shikha Kumari, Shiva Hadi Esfahani, Saeideh Nozohouri, Srinidhi Jayaraman, Nihar Kinarivala, Joanna Kocot, Andrew Baez, Delaney Farris, Thomas J. Abbruscato, Vardan T. Karamyan, Paul C. Trippier
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Editorial Material
Chemistry, Medicinal
Mariateresa Giustiniano, Christian W. Gruber, Caitlin N. Kent, Paul C. Trippier
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Ahmed Morsy, Angelica Carmona, Paul C. Trippier
Summary: Batten disease or neuronal ceroid lipofuscinosis (NCL) is a group of rare fatal inherited neurodegenerative lysosomal storage disorders for which no curative treatments are currently available. Induced pluripotent stem cells (iPSCs) can serve as valuable models to shed light on disease mechanisms and facilitate drug discovery for NCL.
Article
Biochemistry & Molecular Biology
Thomas J. Gardner, J. Peter Lee, Christopher M. Bourne, Dinali Wijewarnasuriya, Nihar Kinarivala, Keifer G. Kurtz, Broderick C. Corless, Megan M. Dacek, Aaron Y. Chang, George Mo, Kha M. Nguyen, Renier J. Brentjens, Derek S. Tan, David A. Scheinberg
Summary: CAR-T cell therapy is a significant breakthrough in cancer treatment, but currently limited to B cell cancers. Challenges include resistance from antigen-negative tumor cells, immunosuppression in the tumor microenvironment, and T cell exhaustion. A novel class of CAR-T cells has been developed to activate a systemically administered small-molecule prodrug in situ at a tumor site to enhance anticancer activity.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Organic
Sravan K. Jonnalagadda, Bader Huwaimel, Shirisha Jonnalagadda, Jered C. Garrison, Paul C. Trippier
Summary: In this study, the synthesis of highly strained fused substituted dihydrobenzopyran cyclopropyl lactones derived from coumarin carboxylates was reported. The substrate scope was found to tolerate a variety of 6- and 8-substituents on the coumarin ring. However, substitution at the 5- or 7-position was resistant to tricyclic lactone formation, except when 7-methyl substitution was present. A plausible mechanism involving intramolecular rearrangement of trans cyclopropyl methyl ketones with phenolic acetate to form a hemiacetal was proposed for the formation of the fused lactone.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Bader I. Huwaimel, Sravan K. Jonnalagadda, Shirisha Jonnalagadda, Shikha Kumari, Alessio Nocentini, Claudiu T. Supuran, Paul C. Trippier
Summary: Inhibition of specific carbonic anhydrase (CA) enzymes is a validated strategy for targeting cancer. CA isoforms IX and XII are overexpressed in human solid tumors and play a critical role in regulating tumor acidification, proliferation, and progression. Novel sulfonamides based on the coumarin scaffold were designed and synthesized as potent and selective CA inhibitors, with some compounds showing high inhibition activity against tumor-associated CA IX and CA XII.
DRUG DEVELOPMENT RESEARCH
(2023)
Editorial Material
Chemistry, Medicinal
Maria-Jesus Blanco, Amanda Bryant-Friedrich, Gunda Georg, Amjad Ali, Paul L. L. Ornstein, Lori Ferrins, Paul C. C. Trippier
Summary: The American Chemical Society Division of Medicinal Chemistry (MEDI) awards achievements in medicinal chemistry through a variety of awards, fellowships, and honors. In celebration of the Gertrude Elion Medical Chemistry Award, the ACS MEDI Division wishes to inform the community about the numerous awards, fellowships, and travel grants available to members.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Editorial Material
Chemistry, Medicinal
Maria-Jesus Blanco, Amanda Bryant-Friedrich, Gunda Georg, Amjad Ali, Paul L. Ornstein, Lori Ferrins, Paul C. Trippier
Summary: The American Chemical Society Division of Medicinal Chemistry (MEDI) bestows a range of awards, fellowships, and honors to acknowledge outstanding contributions in medicinal chemistry. In celebration of the creation of the Gertrude Elion Medical Chemistry Award, the ACS MEDI Division aims to inform the community about the various available awards, fellowships, and travel grants for members.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Krishnaiah Maddeboina, Sravan K. Jonnalagadda, Ahmed Morsy, Ling Duan, Yashpal S. Chhonker, Daryl J. Murry, Trevor M. Penning, Paul C. Trippier
Summary: AKR1C3 is overexpressed in castration-resistant prostate cancer and drives proliferation and aggressiveness by producing androgens. The study reports the optimization of AKR1C3 inhibitors and the discovery of a potent inhibitor, 5r, with high selectivity for AKR1C3. A prodrug strategy was used to improve pharmacokinetics, and the prodrug 4r was converted to the active form, 5r. In vivo experiments showed increased exposure and concentration of 5r compared to direct administration of the free acid. The prodrug 4r effectively reduced tumor volume without toxicity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Louise F. Dow, Alfie M. Case, Megan P. Paustian, Braeden R. Pinkerton, Princess Simeon, Paul C. Trippier
Summary: Enzyme activation has emerged as a new mechanism for therapeutic discovery. This article reviews the identification and advancement of non-kinase enzyme activators and their potential in treating various diseases.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Nihar Kinarivala, Ahmed Morsy, Ronak Patel, Angelica Carmona, Md Sanaullah Sajib, Snehal Raut, Constantinos M. Mikelis, Abraham Al-Ahmad, Paul C. Trippier
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2020)