A new series of 2-heteroarylthio-6-substituted-quinazolin-4-one analogs was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 21, 25, and 39 proved to be active DHFR inhibitors with IC50 range of 0.3-0.8 μM. Compounds 25, 28, 33, 35 and 36 showed broad spectrum antimicrobial activity comparable to the known antibiotic gentamicin. Compound 29 showed broad spectrum antitumor activity toward several tumor cell lines with GI values range of 25.8-41.2%. Molecular modeling studies concluded that recognition with key amino acid Arg38 and Lys31 are essential for binding and biological activities. Flexible alignment; electrostatic and hydrophobic mappings revealed that the obtained model could be useful for the development of new DHFR inhibitors.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejmech.2012.12.061 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A prediction model for electrical strength of gaseous medium based on molecular reactivity descriptors and machine learning method.
J Mol Model
January 2025
Hubei Key Laboratory·for High-Efficiency-Utilization of Solar Energy and Operation, Control of Energy-Storage System, Hubei-University of Technology, Wuhan, 430068, China.
Context: Ionization and adsorption in gas discharge are similar to electrophilic and nucleophilic reactions. The molecular descriptors characterizing reactions such as electrostatic potential descriptors are useful in predicting the electrical strength of environmentally friendly gases. In this study, descriptors of 73 molecules are employed for correlation analysis with electrical strength.
View Article and Find Full Text PDFSubstrate stiffness dictates unique doxorubicin-induced senescence-associated secretory phenotypes and transcriptomic signatures in human pulmonary fibroblasts.
Geroscience
January 2025
Buck Institute for Research On Aging, Novato, CA, 94945, USA.
Cells are subjected to dynamic mechanical environments which impart forces and induce cellular responses. In age-related conditions like pulmonary fibrosis, there is both an increase in tissue stiffness and an accumulation of senescent cells. While senescent cells produce a senescence-associated secretory phenotype (SASP), the impact of physical stimuli on both cellular senescence and the SASP is not well understood.
View Article and Find Full Text PDFInvestigating the decomposition mechanism of DNAN/DNB cocrystal explosive under high temperature using ReaxFF/lg molecular dynamics simulations.
J Mol Model
January 2025
Shanxi Jiangyang Chemical Limited Company, Taiyuan, 030041, Shanxi, China.
Context: DNAN/DNB cocrystals, as a newly developed type of energetic material, possess superior safety and thermal stability, making them a suitable alternative to traditional melt-cast explosives. Nonetheless, an exploration of the thermal degradation dynamics of the said cocrystal composite has heretofore remained uncharted. Consequently, we engaged the ReaxFF/lg force field modality to delve into the thermal dissociation processes of the DNAN/DNB cocrystal assembly across a spectrum of temperatures, encompassing 2500, 2750, 3000, 3250, and 3500 K.
View Article and Find Full Text PDFDefective Mammary Epithelial Outgrowth in Transgenic EKAREV-NLS Mice: Correction via Estrogen Supplementation and Genetic Background Modification.
J Mammary Gland Biol Neoplasia
January 2025
Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Fluorescent biosensors offer a powerful tool for tracking and quantifying protein activity in living systems with high temporospatial resolution. However, the expression of genetically encoded fluorescent proteins can interfere with endogenous signaling pathways, potentially leading to developmental and physiological abnormalities. The EKAREV-NLS mouse model, which carries a FRET-based biosensor for monitoring extracellular signal-regulated kinase (ERK) activity, has been widely utilized both in vivo and in vitro across various cell types and organs.
View Article and Find Full Text PDFOverexpression of FTO alleviates traumatic brain injury induced posttraumatic epilepsy by upregulating NR4A2 expression via m6A demethylation.
Funct Integr Genomics
January 2025
Department of Radiology, The Second Xiangya Hospital of Central South University, No. 139, Renmin Middle Road, Furong District, Changsha City, Hunan Province, 410011, China.
Post-traumatic epilepsy (PTE) is a debilitating chronic outcome of traumatic brain injury (TBI). Although FTO has been reported as a possible intervention target of TBI, its precise roles in the PTE remain incompletely understood. Here we used mild or serious mice TBI model to probe the role and molecular mechanism of FTO in PTE.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!