Research progress on the mechanism of anti-myocardial infarction effect and clinical application of effective components of Salvia miltiorrhiza
This study reviewed the mechanism and clinical application of the main medicinal components ofS. miltiorrhiza in myocardial infarction. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - December 30, 2023 Category: Chemistry Source Type: research
Increased rigidity and bioisosteric replacement in the design, synthesis and preliminary evaluation of novel, functionalized 3,3-dialkyl- γ-butyrolactones as sigma-2 ligands
AbstractThe sigma-2 ( σ2) receptor has been linked to several diseases and conditions including cancer, neuropathic drug addiction, Alzheimer ’s disease, Parkinson’s disease, traumatic brain injury, Niemann-Pick disease, schizophrenia, depression, and anxiety. Targeting σ2 as a means of treating these diseases and conditions has been the subject of intense research, and several clinical trials have been launched to determine the real-world therapeutic utility of this target. Herein, we report the identification of a novel, semirigid series of functionalized 3,3-dialkyl- γ-butyrolactone σ2 ligands, containing pipera...
Source: Medicinal Chemistry Research - December 29, 2023 Category: Chemistry Source Type: research
Synthesis and pharmacological evaluation of novel coumarin based triazolyl glycoconjugates as potential antibacterial and anti-proliferative agents
AbstractA library of novel coumarin-based triazolyl glycoconjugates is prepared and screened for in vitro antibacterial activity against Gram-positive (Bacillus megaterium) and Gram-negative bacteria (Escherichia coli)via disc diffusion technique in the current study. The biological assays revealed significant antibacterial potential of new synthetic coumarin triazolyl glycoconjugates, compound5d being the most active one with zones of inhibition (mm) of 34.33  ± 0.88 (10 μg/mL) and 36.66 ± 0.88 (20 μg/mL) againstE. coli and 17.66  ± 1.20 (10 μg/mL) and 20 ± 1.15 (20 μg/mL) againstB. megater...
Source: Medicinal Chemistry Research - December 28, 2023 Category: Chemistry Source Type: research
Self-assembled amphiphilic bipyridine and bisquinoline cisplatin analogues: synthesis and anticancer properties
We report the synthesis and characterisation of two amphiphilic cisplatin analogues derived from bipyridine and bisquinoline modified with two 3-oxo-3,6,9,12-tetraoxadocosyl groups. The amphiphilic cisplatin analogues readily form vesicles in water such as 200 to 400  nm in diameter for the bipyridine Pt complex and 1000 to 1300 nm in diameter for the bisquinoline Pt complex. The bisquinoline Pt complex exhibited a LD50 of ~24  µM for HeLa and HEK cells. On the other hand, the Pt-bipyridine complex exhibited no notable toxicity against HeLa and HEK cells under 121 µM. Amphiphilic cisplatin analogues of this type ...
Source: Medicinal Chemistry Research - December 23, 2023 Category: Chemistry Source Type: research
Bioactivities and the structural modification of Parthenolide: a review
AbstractParthenolide, a sesquiterpene lactone derived from Feverfew (Tanacetum parthenium) buds, has attracted significant attention due to its versatile pharmacological potential. It and its derivatives exhibit a range of bioactivities, including antibacterial, anti-leukemia, anticancer, and anti-inflammatory effects. Current research focuses on the structural modifications of parthenolide, exploring how alterations impact its bioactivity. This review aims to provide an overview of recent studies involving parthenolide ’s structural modifications and their corresponding impact on its biological functionality. By examini...
Source: Medicinal Chemistry Research - December 23, 2023 Category: Chemistry Source Type: research
A concise review on anti-breast cancer effectiveness of s-triazines through EGFR kinase inhibition
AbstractToday, one of the most common malignancies in women is breast cancer. Despite the large number of commercially available anticancer drugs, cancer cannot be cured without leaving adverse effects. The MCF-7, a human breast cancer cell line, has been the subject of the most research globally. Similarly, overexpression of the EGFR protein increases cell proliferation and decreases cell death or apoptosis. This can stimulate several downstream signaling pathways. Therefore, novel drugs against cancer with improved selectivity and specificity are required to overcome the limitations of present therapy. Thes-triazine deri...
Source: Medicinal Chemistry Research - December 21, 2023 Category: Chemistry Source Type: research
Design, synthesis and evaluation of aurone and indanone derivatives as novel antitumor agents
AbstractAn aurone derivative HJ-1, was isolated fromCoreopsis tinctoria in our previous work, showed potential anti-hepatocellular carcinoma activity. From it, seventy-five compounds were synthesized via bioisostere and scaffold hopping strategy, and then submitted to the inhibitory activities evaluation against four tumor cells (HELA, HT-29, A549 and HepG2) through MTT assays. These activities have been discussed in SAR. Based on the results, compounds, thirty compounds showed moderate to good antitumour activity. Among them, five compounds (A3: 3.41  ± 1.03 μM, E3: 5.11 ± 0.23 μM, E8: 4.14 ± 1.21 Î...
Source: Medicinal Chemistry Research - December 20, 2023 Category: Chemistry Source Type: research
Design, synthesis, molecular docking, and biological activity of pyrazolo[3,4-b]pyridines as promising lead candidates against Mycobacterium tuberculosis
AbstractPyrazolo[3,4-b]pyridine is a medicinally privileged structure. We have achieved a new and facile synthesis of a combinatorial library of its tetra- and persubstituted derivatives by trifluoracetic acid catalyzed condensation of a group of 5-aminopyrazoles and a group of α-oxoketene dithioacetals. Furthermore, we demonstrated structural modification of the products via reductive desulfurization, hydrolysis of the ester, and Suzuki coupling of the bromo derivative with aryl boronic acids. Some products were subjected to in vitro Microplate Alamar Blue assay (MABA) a ssay againstM. tuberculosis H37Rv strain and in si...
Source: Medicinal Chemistry Research - December 19, 2023 Category: Chemistry Source Type: research
Pyrrolobenzodiazepines: natural sources, therapeutic uses, and future in neurological treatments
AbstractPyrrolobenzodiazepines (PBDs) are a potent class of compounds that have been analyzed since the 1960s and are found naturally in a wide variety of species. They may be obtained through extraction from natural sources or through synthetic routes. A variety of studies have indicated remarkable anti-tumor, anti-bacterial, analgesic, and anti-neurodegenerative activities of PBDs. This review will examine natural sources of PBDs, their biological activities, newer synthesis strategies, and the effect of structural modifications, specifically from a neurological standpoint. Emerging studies on pyrrolobenzodiazepines offe...
Source: Medicinal Chemistry Research - December 18, 2023 Category: Chemistry Source Type: research
Indazole derivatives as novel inhibitors of monoamine oxidase and D-amino acid oxidase
AbstractThe monoamine oxidase (MAO) enzymes metabolize neurotransmitter amines in the peripheral and central tissues, and inhibitors of these enzymes find application in the treatment of neuropsychiatric and neurodegenerative disorders. Based on reports that the neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole, inhibits the MAO-B isoform, the present study investigated the MAO inhibition potencies of a synthetic series of fifteen C5- and C6-substituted indazole derivatives. While only one derivative (5c) was a submicromolar inhibitor of human MAO-A (IC50 = 0.745 µM), all compounds inhibited human MAO...
Source: Medicinal Chemistry Research - December 15, 2023 Category: Chemistry Source Type: research
Computer-aided design, synthesis and evaluation of new SARS-CoV-2 Mpro inhibitors based on 1,5,6,7-tetrahydro-4H-indazol-4-one scaffold
AbstractA novel class of SARS-CoV-2 main protease (Mpro) inhibitors derived from 1,5,6,7-tetrahydro-4H-indazol-4-ones was designed. Virtual screening based on molecular docking followed by molecular dynamics simulation and MM/GBSA calculations was used for selecting compounds for synthesis and an evaluation. After testing 29 prepared compounds for activity against Mpro, two hits with IC50 values bellow 60  μM were found with the best result of 27.31 μM for racemic amide9m. SAR and further possibilities for hit optimization were discussed. The effectiveness of different approaches (MM/GBSA and alchemical ABFE) for pro...
Source: Medicinal Chemistry Research - December 11, 2023 Category: Chemistry Source Type: research
Discovery of novel fatty acid amide hydrolase (FAAH) inhibitors as anti-Alzheimer ’s agents through pharmacophore-based virtual screening, molecular docking and experimental validation
AbstractAlzheimer ’s disease (AD) is the most prevalent form of neurodegenerative condition distinguished by the deposition of amyloid beta plaques and neurofibrillary tangles in the brain with a progressive decline of cognition abilities. Unfortunately, none of the existing treatments has the ability to cure the d isease. The biggest challenge in drug development for AD is its obscurity pertaining to underlying pathophysiology. The endocannabinoid system (ECS) has recently emerged as a critical target through the inhibition of the enzyme fatty acid amide hydrolase (FAAH) which gives protective effects in the context of ...
Source: Medicinal Chemistry Research - December 9, 2023 Category: Chemistry Source Type: research
FTase inhibitors and cancer: prospects for use in targeted therapies
AbstractFarnesyltransferase (FTase) is a key enzyme that catalyzes the farnesylation of Ras protein. It is used to bind RAS protein to plasma membrane to complete signal transduction. Ras has been shown to be closely related to the development of many cancers. In recent years, FTase has been studied more deeply as an anticancer target. And more and more novel FTase inhibitors have been reported for the treatment of pancreatic cancer, lung cancer, colon cancer, HGPS, PL and so on. This review summarizes the structural features and biological activities of various novel FTase inhibitors reported since 2013. The reported nove...
Source: Medicinal Chemistry Research - December 9, 2023 Category: Chemistry Source Type: research
Enantioselectivity of pinene against Leishmania amazonensis
This study aimed to investigate the activity of pinene enantiomers against the HTL causative agent,Leishmania amazonensis. The parasite viability was determined using the resazurin assay and transmission electron microscopy. The most active enantiomers against promastigotes and amastigotes were (+)- α-pinene and (+)-β-pinene with IC50 ranging from 14 to 110  µg/mL. Furthermore, the positive enantiomers exhibited moderate cytotoxicity against the RAW 264.7 cell line and sheep erythrocytes and desirable selectivity indexes exceeding 10. In addition, in silico toxicological analysis revealed a pinene enantiomer profile s...
Source: Medicinal Chemistry Research - November 25, 2023 Category: Chemistry Source Type: research
Characterization of novel angiotensin-I converting enzyme inhibitory peptides derived from Taiwan red quinoa (Chenopodium formosanum Koidz.) seed proteins using two sequential bioassay-guided fractionations
AbstractTaiwan red quinoa (Chenopodium formosanum Koidz.) is a pseudo-cereal crop native to Taiwan with a rich protein content that can potentially be a bioactive peptide precursor, such as angiotensin-I converting enzyme inhibitory (ACEI) peptides. Taiwan red quinoa seed protein (TRQSP) thermolysin hydrolysate showed a relatively potent ACE IC50 value of 58.5  µg/mL. After two sequential bioassay-guided fractionations, fraction F4.3 showed the best ACEI activity (89.3%). Liquid chromatography-tandem high-resolution mass spectrometry (LC-HRMS) incorporated with de novo peptide sequencing and database searching were perf...
Source: Medicinal Chemistry Research - November 23, 2023 Category: Chemistry Source Type: research
