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Glutamine‐addicted cancer metabolism is recently recognized as novel cancer target especially for KRAS and KEAP1 co‐occurring mutations. To identify more drug‐like GLS inhibitors, we report the amides in the wing macrocycles for GLS inhibition with unique SAR analysis. Although the amidotriazoles (amides in the wing) are in general less potent than those of acylaminothiadiazole analogs (reverse amides in the wing), macrocycle 4, 5, and 7 are selected as a potent macrocyclic GLS inhibitor in both biochemical and cell viability assays. Selected molecules result in partial reduction in intracellular glutamate levels in LR (LDK378‐resistant) cells which is consistent to their cells viability result. Finally, selected compounds reduce the growth of A549 and H460 cells which have co‐occurring mutations including KRAS and KEAP1. The putative binding mode of macrocycle 4 is also suggested using a molecular docking model. [ABSTRACT FROM AUTHOR]

Background: Since severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was first reported in Wuhan, China, in December 2019, it has spread rapidly, and many coronavirus disease (COVID‐19) cases have occurred in Gwangju, South Korea. Viral mutations following the COVID‐19 epidemic have increased interest in the characteristics of epidemics in this region, and pathogen genetic analysis is required for infection control and prevention. Methods: In this study, SARS‐CoV‐2 whole‐genome analysis was performed on samples from patients with COVID‐19 in Gwangju from 2020 to 2022 to identify the trends in COVID‐19 prevalence and to analyze the phylogenetic relationships of dominant variants. B.41 and B.1.497 prevailed in 2020, the early stage of the COVID‐19 outbreak; then, B.1.619.1 mainly occurred until June 2021. B.1.617.2, classified as sublineages AY.69 and AY.122, occurred continuously from July to December 2021. Since strict measures to strengthen national quarantine management had been implemented in South Korea until this time, the analysis of mutations was also able to infer the epidemiological relationship between infection transmission routes. Since the first identification of the Omicron variant in late December 2021, the spread of infection has been very rapid, and weekly whole‐genome analysis of specimens has enabled us to monitor new Omicron sublineages occurring in Gwangju. Conclusions: Our study suggests that conducting regional surveillance in addition to nation‐level genomic surveillance will enable more rapid and detailed variant surveillance, which will be helpful in the overall prevention and management of infectious diseases. [ABSTRACT FROM AUTHOR]

Methyl benzimidazole-2-carbamate anthelmintics are a class of oral drugs to treat parasitic worm infections via microtubule disruption for non-systemic indications and currently in use. In order to use for anticancer treatment, the new benzimidazoles needs to improve solubility and pharmacokinetic parameters while maintaining its cellular potency as for systemic drug. Structure-activity-relationship on the benzimidazole is thoroughly examined and a novel benzimidazole-2 propionamide BNZ-111 is identified having good oral exposure and bioavailability in rat. Molecular docking study suggests BNZ-111 have a specific binding mode to the β subunit of curved tubulin. BNZ-111 is potent to cancer cells and possesses good drug-like properties as oral drug. Especially, BNZ-111 is not a P-gp substrate and it demonstrates its efficacy over Paclitaxel-resistance tumor in vivo., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Lateral spinal artery (LSA) aneurysms are extremely rare lesions that can rupture and cause subarachnoid hemorrhage (SAH) even though the spinal arteries communicate directly with the subarachnoid space. To date, six cases of LSA aneurysms have been reported in the literature. Herein, three such cases are reported. All patients presented to the emergency department with headaches. The patients in the first two cases were confirmed to have SAH and LSA aneurysms on a brain computed tomography (CT) angiography performed at the hospital. Two patients had prior instances of cerebral infarction and coronary disease, respectively, and were undergoing antiplatelet therapy. The antiplatelet medication was stopped for 2 weeks and 1 week, respectively, while conservative care was provided. Subsequently, a suboccipital craniectomy was performed, followed by aneurysm clipping. Following the surgery, both patients were discharged without any significant neurological deficits. Regarding the third patient, no aneurysm was found on brain CT angiography, and cerebral angiography was performed during the patient's hospital stay. She was hospitalized, where she received medication and conservative care, and was discharged with an improvement in bleeding without neurological symptoms. Subsequently, a LSA aneurysm was identified on a brain CT angiography performed at an outpatient clinic; however, the patient was transferred because she wanted to be treated at another hospital. LSA aneurysms are difficult to visualize using CT angiography; therefore, careful angiographic studies are required. Surgical clipping is the treatment of choice if the aneurysm is inaccessible by the endovascular treatment.