Selectivity of N(2)-substituted oxotriazinoindole aldose reductase inhibitors is determined by the interaction pattern with Pro301-Arg312 loop of aldehyde reductase
AbstractNovel oxotriazinoindoles (OTIs) were recently reported as highly efficient and selective aldose reductase inhibitors. Here, a series of novelN(2)-substituted oxotriazinoindoles was developed with the aim to investigate molecular interactions within the aldose reductase (ALR2) inhibitor binding site. About twice increased inhibition efficacy of the most efficient derivative14 (N(2)-CH2CH2COOH) compared to the unsubstituted leadOTI was obtained, yet at the expense of selectivity relative to anti-target aldehyde reductase (ALR1). To explain the major drop in selectivity, observed also in otherN(2)-substituted derivati...
Source: Medicinal Chemistry Research - February 14, 2024 Category: Chemistry Source Type: research
Novel biologically active pyridine derivatives: Synthesis, structure characterization, in vitro antimicrobial evaluation and structure-activity relationship
AbstractThe rate of microbial resistance has continued to rise significantly as the availability of new antibiotics has declined. A new series of pyridine and thienopyridine derivatives were designed, synthesized and tested as antimicrobial agents. The reaction of 4-bromo acetophenone and vetraldehyde (3,4-dimethoxy benzaldehyde) in ethanol and sodium hydroxide solution afforded the corresponding chalcone which was used as a suitable precursor to prepare a new series of pyridine derivatives. The treatment of the latter chalcone with 2-cyanothioacetamide afforded the corresponding pyridinethione which was used as a precurso...
Source: Medicinal Chemistry Research - February 14, 2024 Category: Chemistry Source Type: research
Benzocaine-N-acylindoline conjugates: synthesis and antiviral activity against Coxsackievirus B3
AbstractIndoline-5-sulfonamide derivatives of benzocaine have been synthesized using a sequence of three reactions:N-acylation, sulfochlorination, sulfonamidation, and their antienteroviral activity has been evaluated. Two compounds, namely, ethyl 4-((1-(cyclobutanecarbonyl)indoline)-5-sulfonamido)benzoate and ethyl 4-((1-benzoylindoline)-5-sulfonamido)benzoate exhibited a medium level of activity against coxsackievirus B3 (Nancy strain) in vitro. Their antiviral potential is exerted upon prophylactic application when added to cell culture before infection with the virus. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - February 13, 2024 Category: Chemistry Source Type: research
Exploring the latest breakthroughs in rhodesain inhibitors for African trypanosomiasis
AbstractHuman African Trypanosomiasis is a serious public health concern, and new chemical therapeutic agents need to be developed to combat this disease. Rhodesain (RhD) inhibitors have shown promising results in medicinal chemistry, specifically againstTrypanosoma brucei. These inhibitors target the cysteine protease RhD, which is essential for the survival ofT. brucei. However, as the pharmaceutical industry lacks interest in these inhibitors, the development of drugs based on them is challenging. In this review, we showed the impact of RhD inhibitors on medicinal chemistry in the past 10 years (2013 –2022), particula...
Source: Medicinal Chemistry Research - February 2, 2024 Category: Chemistry Source Type: research
Unveiling the potential of prodrug and drug-conjugate strategies in treatment of diabetes mellitus and its complications
AbstractThe 2021 statistics from the International Diabetes Federation reveals that approximately 537 million adults between the ages of 20 and 79 are currently coping with diabetes, highlighting the pressing demand for innovative treatments. To expedite this process, it is crucial to learn from previous failures in drug development. One established method for enhancing the biological, pharmacokinetic or the physicochemical properties of potent drug candidates is through the use of prodrugs. Prodrugs have demonstrated their effectiveness in surmounting challenges related to a drug ’s efficacy during the phases of drug re...
Source: Medicinal Chemistry Research - January 29, 2024 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 - January 27, 2024 Category: Chemistry Source Type: research
Synthesis of adamantane-monoterpene conjugates with 1,3,4-thiadiazol-2(3H)-imine linker and evaluation of their inhibitory activity against TDP1
AbstractTyrosyl-DNA phosphodiesterase 1 (TDP1) is a DNA repair enzyme that can reduce the efficacy of some anticancer drugs targeting topoisomerase 1 (TOP1) making it a promising target for antitumor therapy when combined with TOP1 poisons. Here we describe the synthesis of a number of adamantane-monoterpene conjugates20a –g and21a –g connected through a 1,3,4-thiadiazol-2(3H)-imine linker, where acyclic, monocyclic, and bicyclic structural types of monoterpenes were used. All the synthesized compounds demonstrated activity against TDP1 in micromolar range, with the most potent inhibitor being compound21a (IC50 1.2 ...
Source: Medicinal Chemistry Research - January 27, 2024 Category: Chemistry Source Type: research
Polyketides from Neohelicosporium griseum: structure assignment and bioactivity investigation
AbstractIn the pursuit of discovering new active metabolites from helicosporous hyphomycetes, rice fermentation products ofNeohelicosporium griseum were examined. Eight compounds were isolated from this saprophytic fungus, namely vertixanthone (1), diaportheone A (2), 1,3,6,8-tetrahydroxyanthraquinone (3), lecanoric acid (4), decarboxycitrinone (5), 6,8-dihydroxy-4-hydroxymethyl-3,5-dimethyl-isochromen-1-one (6), decarboxyhydroxycitrinone (7), and ergosterin (8). The 1D and 2D NMR characteristics of compound1 in DMSO-d6 were detailed for the first time. Antimicrobial testing indicated that compounds1–4 exhibited moderate...
Source: Medicinal Chemistry Research - January 27, 2024 Category: Chemistry Source Type: research
Indazole derivatives as selective inhibitors of butyrylcholinesterase with effective blood-brain-barrier permeability profile
AbstractAlzheimer ’s disease (AD) is a chronic disease that is multifactorial. Its underlying cause and mechanisms are yet to be fully understood and numerous research are underway to develop more effective drug candidates. This research explores the synthesis of an indazole-containing novel drug targeting AD, part icularly by inhibiting cholinesterase activity. Among the 17 indazole derivatives synthesized in this study, compound4q was demonstrated to have potent and selective butyrylcholinesterase (BChE) inhibitory activity. Molecular docking simulations revealed that the binding of4q with BChE was through hydrophobic ...
Source: Medicinal Chemistry Research - January 27, 2024 Category: Chemistry Source Type: research
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 - January 27, 2024 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 - January 27, 2024 Category: Chemistry Source Type: research
Rehmannia glutinosa polysaccharides: a review on structure-activity relationship and biological activity
This article will lay the foundation for the future development and clinical application research of functional products ofRehmannia glutinosa. It also has certain guiding significance for the development and application of traditional Chinese medicine resources ofRehmannia glutinosa. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - January 27, 2024 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 - January 27, 2024 Category: Chemistry Source Type: research
Identification of α-mangostin as a potent inhibitor of β-lactamase OXA-48
In this study, we investigated the inhibitory potential of α-mangostin against OXA-48 with an IC50 value of 0.52 μM. Enzyme activity assays demonstrated that α-mangostin inhibited OXA-48 reversibly through a non-competitive and dose-dependent inhibition mode. The docking analysis revealed that the 7-hydroxyl group of α-mangostin formed hydrogen bonds with Thr197 and Trp222, whereas the 5-hydroxyl group a nd the 4-carbonyl group interacted with Lys116 and Met115. Our study indicates that α-mangostin exhibits significant inhibition against OXA-48 and holds promise as a potential compound for the development of β-lac...
Source: Medicinal Chemistry Research - January 27, 2024 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 - January 27, 2024 Category: Chemistry Source Type: research
