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 12, 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 10, 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 10, 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 4, 2024 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 - January 1, 2024 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 - January 1, 2024 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 - January 1, 2024 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 - January 1, 2024 Category: Chemistry Source Type: research
Kaempferia diterpenoids and flavonoids: an overview on phytochemistry, biosynthesis, synthesis, pharmacology, and pharmacokinetics
AbstractKaempferia species have contained various crucial ethnobotanical features, and are being used as traditional folk medicines in some Southeast Asia. This review tends to highlight important information (phytochemistry, biosynthesis, synthesis, pharmacology, and pharmacokinetics) ofKaempferia principal phytochemical classes diterpenoids and flavonoids. The electronic sources, e.g., Google Scholar, Sci-Finder, and Web of Science, and the most meaningful keywords “Kaempferia”, “diterpenoids”, and “flavonoids” have been more often utilized for searching the literature. More than 190 phytochemicals type diter...
Source: Medicinal Chemistry Research - January 1, 2024 Category: Chemistry Source Type: research
Design, synthesis, and in silico studies of novel di-(2-aryl hydrozonopropanal) arene derivatives as potent anticancer for targeting A2AR and LRP6 in HCT116 cell
This study aimed to design and synthesize novel anticancer drug candidates and then examine their anticancer activity against human cancer cell lines. The anti-proliferation of human colon cancer cells (HCT116) was examined using the MMT assay and compared to the activity of doxorubicin as chemotherapy after characterizing novel derivatives of di (2-aryl hydrazonopropane) arene by elemental analyzer, FTIR, 1H, 13C NMR, and ESI-MS. Chemoinformatic tools predicted their targets, and then molecular docking was performed to predict the binding affinity of compounds to the main receptors expressed in colon cancer: the adenosine...
Source: Medicinal Chemistry Research - January 1, 2024 Category: Chemistry Source Type: research
Design and synthesis of novel cycloalkanecarboxamide parabanic acid hybrids as anticonvulsants
AbstractAiming to develop novel anticonvulsant agents a new series of novel cycloalkanecarboxamide parabanic acid hybrids series8,9 and10 possessing the essential structure requirements for anticonvulsant activity was synthesized starting from cycloalkanones. All final target compounds were primary screened for chemically and electrically induced seizures using pentylenetetrazole “scPTZ” and maximal electroshock seizure “MES” models. In phase I anticonvulsant evaluation compounds8b and10b exhibited the highest potency among all the target compounds with 100% protection towards chemically induced seizures. Results o...
Source: Medicinal Chemistry Research - January 1, 2024 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 - January 1, 2024 Category: Chemistry Source Type: research
One-pot synthesis and in vitro bioactivity of novel 4-aminopyrazolo[3,4-b]pyridine derivatives as potential antimicrobial compounds
AbstractThe present paper describes an efficient synthesis of a series of 4-aminopyrazolo[3,4-b]pyridine derivatives11a –i in 69 –81% yields by one-pot three-component domino reaction of phenylhydrazine and two differentβ-ketonitriles in DMSO. All the synthesized derivatives were screened in vitro for their antimicrobial potential against seven Gram-positive and Gram-negative clinical bacterial strains and one fungal strain. Most of the tested derivatives displayed promising antimicrobial potency and activity was found to be comparable to standard drugs (amoxicillin and fluconazole). Compounds11a and11d with the MIC v...
Source: Medicinal Chemistry Research - January 1, 2024 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 - January 1, 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 - December 30, 2023 Category: Chemistry Source Type: research
