Memantine derived compounds as potent in vitro inhibitors of urease: Repurposing of memantine, sonication assisted derivatization and in vitro enzyme inhibition, kinetics and molecular docking studies
AbstractThe phenyl-substituted thiourea derivatives (2-21) of memantine (1) were synthesized through a sonication-assisted single-step chemical reaction. Urease inhibition and cytotoxicity against 3T3 mouse fibroblast cells were also performed. The synthesized compounds were characterized using UV/VIS, FT-IR,1H-NMR,13C-NMR (BB, DEPT-90, DEPT-135), and mass spectrometric techniques. All of these compounds were found to be new, except2,14,17, and21. These compounds showed good activity against the urease (IC50 = 36.5 ± 0.20 to 5.6 ± 0.30 µM) while acetohydroxamic acid (AHA) was used as a standard (IC50 =â€...
Source: Medicinal Chemistry Research - January 27, 2023 Category: Chemistry Source Type: research
Medicinal uses, phytochemistry, pharmacology, and taxonomy of Poygonum aviculare L.: a comprehensive review
AbstractPolygonum aviculare is a plant widely distributed in all continents and very common in temperate regions of the world. The different parts of this plant are used as an anthelmintic, antidiabetic and to treat kidney disorders and skin problems. In order to highlight the importance ofP. aviculare L., This review is undertaken with the aim to highlight some aspects of this plant, specifically the taxonomy, ethnomedicinal, morphological, phytochemical and biological studies of the plant. The taxonomic analysis indicated that the plant is descended from an inbred line and the cytogenetic results showed thatP. aviculare ...
Source: Medicinal Chemistry Research - January 25, 2023 Category: Chemistry Source Type: research
Synthesis, cytotoxicity, Pan-HDAC inhibitory activity and docking study of new N-(2-aminophenyl)-2-methylquinoline-4-carboxamide and (E)-N-(2-aminophenyl)-2-styrylquinoline-4-carboxamide derivatives as anticancer agents
In this study, new cytotoxic agents based on 2-aminobenzamide scaffold were designed, synthesized and evaluated against A549, HCT116 and HT-29 cancer cell lines (inhib%) in doses of 5  μM and 20 μM that displayed moderate to good effects. The synthesized compounds were evaluated for their inhibitory activity (inhib%) against Pan-HDAC on HCT116 and HT-29 cell lines which displayed inhibitory activity (%) of 0–67.34% on HT-29 and 5.67–50.18% on HCT116 cell line at concent rations of 100 μM. Generally, Pan-HDAC inhibitory activity (inhib%) in (E)-N-(2-aminophenyl)-2-styrylquinoline-4-carboxamide series was better...
Source: Medicinal Chemistry Research - January 24, 2023 Category: Chemistry Source Type: research
Novel Benzo[4,5]imidazo[1,2-a]pyrimidine derivatives as selective Cyclooxygenase-2 Inhibitors: Design, synthesis, docking studies, and biological evaluation
AbstractThe present study was aimed at the synthesis and evaluation of a new series of benzo[4,5]imidazo[1,2-a]pyrimidine having a methylsulfonyl group as COX-2 (cyclooxygenase-2) inhibitor pharmacophore. Molecular modeling studies were performed using the Autodock program, and the results demonstrated that methylsulfonyl pharmacophore was adequately placed into the COX-2 active site. The in vitro and in vivo COX-2 inhibitory effects were also evaluated. In the in vitro assay, all newly synthesized compounds showed moderate to good selectivity for the inhibition of the COX-2 enzyme. However, compound 2-(4-(methylsulfonyl) ...
Source: Medicinal Chemistry Research - January 23, 2023 Category: Chemistry Source Type: research
Mannose: a potential saccharide candidate in disease management
AbstractThere are a plethora of antibiotic resistance cases and humans are marching towards another big survival test of evolution along with drastic climate change and infectious diseases. Ever since the first antibiotic [penicillin], and the myriad of vaccines, we were privileged to escape many infectious disease threats. The survival technique of pathogens seems rapidly changing and sometimes mimicking our own systems in such a perfect manner that we are left unarmed against them. Apart from searching for natural alternatives, repurposing existing drugs more effectively is becoming a familiar approach to new therapeutic...
Source: Medicinal Chemistry Research - January 20, 2023 Category: Chemistry Source Type: research
α-Glucosidase and cholinesterase inhibiting potential of a series of semisynthetic nitrogen triterpenic derivatives
In this study, a series of 40 semisynthetic nitrogen triterpenic derivatives of lupane, oleanane and ursane type including 33 previously synthesized and 7 new compounds were synthesized and screened to determine their ability to act as inhibitors for the enzymesα-glucosidase (fromS. saccharomyces), acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum). As a result, 17 out of 40 compounds demonstrated significant inhibitory properties towardα-glucosidase with IC50 values not exceeding 10  μM with IC50 178.25  µM for acarbose as a reference. A-azepano-28-cinnamoyloxy-eryth...
Source: Medicinal Chemistry Research - January 19, 2023 Category: Chemistry Source Type: research
Novel vitamin K3 analogs containing 3-N-substituted aromatic and piperazine rings with selective in vitro anticancer activity against HeLa, U87 MG, and MCF-7 cells
In this study, firstly, novel vitamin K3 analogs were synthesized by the reactions of vitamin K3 (2-methyl-1,4-naphthoquinone, also known as menadione) with some aromatic and heterocyclic ring substituted nucleophiles such as 2,4-dimethoxyaniline, 4-methoxyaniline, 4-benzylpiperidine and 1-(2-aminoethyl)piperazine in ethanol/Na2CO3, and 1-(diphenylmethyl)piperazine in chloroform/triethylamine (TEA) at room temperature. Their structures were elucidated by Fourier transform infrared spectroscopy (FT-IR),1H nuclear magnetic resonance (1H NMR), attached proton test nuclear magnetic resonance (APT-NMR) and mass spectrometry (MS...
Source: Medicinal Chemistry Research - January 18, 2023 Category: Chemistry Source Type: research
Engelheptanoxides behave as liver X receptor α agonists
In this study, the activity of engelheptanoxide A and C against LXR α was evaluated by the transient transfection reporter and mammalian one-hybrid assays. The results showed that engelheptanoxide A and C respectively transactivated CYP7A1, ABCA1, and Gal4 promoters in the dose-dependent manner. Furthermore, the docking study demonstrated that engelheptanoxide A an d C can contact with the LXRα ligand binding pocket in the similar manner as 22(R)-hydroxycholesterol, an endogenous LXRα agonist, to agonize LXRα. These results indicated thatEngelhardia roxburghiana might be able to exert pharmacological effects through LX...
Source: Medicinal Chemistry Research - January 13, 2023 Category: Chemistry Source Type: research
Rational design and development of novel NAE inhibitors for the treatment of pancreatic cancer
AbstractPancreatic cancer remains clinically challenging because of the lack of efficient targeted therapies and high aggressiveness. NEDD8 activating enzyme (NAE) plays a critical role in various cellular functions in cancers. Herein, we report the synthesis, optimization, and evaluation of a new series of pyrido[2,3-d]pyrimidin-7(8H)-one derivative as highly selective and efficacious NAE inhibitors, enabling rapid degradation of related substrates and potent inhibition of BxPC-3 cell proliferation. Moreover, western blot assays demonstrated that compound51 could inhibit NAE activity, resulting in apoptosis in BxPC-3 cell...
Source: Medicinal Chemistry Research - January 12, 2023 Category: Chemistry Source Type: research
Correction: Design, synthesis, and antimicrobial evaluation of novel 10-Undecenoic acid-based lipidic triazoles
(Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - January 4, 2023 Category: Chemistry Source Type: research
Novel fluorinated pyrazole-based heterocycles scaffold: cytotoxicity, in silico studies and molecular modelling targeting double mutant EGFR L858R/T790M as antiproliferative and apoptotic agents
AbstractHepatocellular carcinoma (HCC), also known as hepatoma, is the most prevalent type of primary liver cancer. It begins in the hepatocytes, the liver ’s major cell type. Cancer that began in another region of the body but has spread to the liver is known as secondary cancer of life; several still unmet demands for better, less toxic therapy to treat this malignant tumor. Several novel pyrazolo[1,5-a]pyrimidine derivatives were synthesized as part of our goal to develop promising anticancer drugs. All the synthesized hybrids have been screened for their cytotoxicity effect against three cancer cell lines which are; ...
Source: Medicinal Chemistry Research - January 2, 2023 Category: Chemistry Source Type: research
Design, synthesis and evaluation of salicylic acid-donepezil hybrids as functional agents for the treatment of Alzheimer ’s disease
AbstractIn this work, a series of salicylic acid derivatives was designed through the multi-target-directed ligand strategy (MTDLs). The synthesized compounds were evaluated as multifunctional agents. The in vitro biological activity results revealed that compound3a was a selectiveeqBuChE inhibitor (IC50 = 0.29 μM), compound3k was a selectiveeeAChE inhibitor (IC50 = 0.77 μM), and compound3p was a selectiveeqBuChE inhibitor (IC50 = 0.82 μM). Compounds3a,3k and3p also showed good antioxidant activity and anti-inflammatory property. Furthermore, compounds3a,3k and3p were selective metal chelators. Moreove...
Source: Medicinal Chemistry Research - January 2, 2023 Category: Chemistry Source Type: research
Medicinal chemistry insights into non-hydroxamate HDAC6 selective inhibitors
AbstractHDAC6 is predominantly found in the cytoplasm and is mainly responsible for deacetylation of non-histone proteins including α-tubulin in microtubules, the HSP90 chaperone, cortactin, etc. Inhibition of HDAC6 has been shown to be efficacious in treating cancer, neurodegenerative diseases, heart failure, pain, fibrosis, and inflammatory diseases. This review focuses on the recent more drug-like selective HDAC6 inhibitors, especially the two major chemotypes of mercaptoacetamides and fluoroalkyl-oxadiazoles. The latter class lacks structural alert thus has low potential for toxicities. As a consequence, fluoroalkyl-o...
Source: Medicinal Chemistry Research - January 1, 2023 Category: Chemistry Source Type: research
Optimization of clofibrate with natural product sesamol for reducing liver injury induced by acetaminophen
AbstractAcetaminophen (APAP), which is widely used for the treatment of analgesic-antipyretic as the first-line drug, can cause extensive hepatic injury and even acute hepatic failure. Oxidative stress and inflammation have been considered as the main mechanism of hepatotoxicity. However, the only antidote available for clinical application is N-acetylcysteine at present, but it has side effects and may have no effect after a high dose. Although other reported compounds have detoxification effects, which suffer from problems caused by the relatively high dose, unclear mechanisms, or being evaluation. In order to obtain a b...
Source: Medicinal Chemistry Research - January 1, 2023 Category: Chemistry Source Type: research
Synthesis and bioactivity evaluation of pachymic acid derivatives as potential cytotoxic agents
In this study, 18 derivatives of pachymic acid were synthesized by modifying their molecular structures and evaluated for their anticancer activity against two human cancer cell lines using the CCK-8 assay. Structure-activity relationship studies according to the in vitro cytotoxicity unexpectedly found one promising derivativeA17 (namely tumulosic acid, also found inPoria cocos), which had stronger anti-proliferative activity than the positive drug cisplatin against HepG2 and HSC-2 cell lines with IC50 values of 7.36  ± 0.98 and 2.50 ± 0.15 μM, respectively. Further pharmacological analysis demonstrated thatA...
Source: Medicinal Chemistry Research - December 29, 2022 Category: Chemistry Source Type: research
