Synthesis of amide warhead containing coumarin derivatives as potential pancreatic lipase inhibitors: in silico and in vitro evaluation for obesity treatment
AbstractA series of coumarin-3-carboxamide analogues has been designed, synthesized and assessed for their ability to inhibit pancreatic lipase (PL). Amongst all the synthesized analogues5q,5k and 5c exhibited potential PL inhibition activity with IC50 values of 19.41, 21.30 and 24.90 µM, respectively when compared to orlistat (IC50 = 0.97 µM). Analogue5q was found to inhibit PL with IC50 value of 19.41 µM and in a competitive manner with an inhibition constant (Ki) of 10.386 µM. Further, the docking study confirmed the interaction of analogue5q (MolDock score of −113.845 kcal mol−1) with importa...
Source: Medicinal Chemistry Research - July 28, 2023 Category: Chemistry Source Type: research
Using molecular networking and docking to explore arginase inhibitors among Drimys brasiliensis chemical constituents
This study has investigated whether the bark and leaves ofDrimys brasiliensis Miers (Winteraceae), a plant known for its antileishmanial effect, can inhibitLeishmania amazonensis arginase. IC50 values of 13.6 and 8.0 μg/mL were obtained for the ethanolic extracts fromD. brasiliensis bark and leaves, respectively. Liquid chromatography –high resolution mass spectrometry analysis of the bioactive extracts helped to identify ten compounds, including flavonoids, phenolic acids, and hydroxycinnamic acid derivatives. Among these compounds, flavonoids and chlorogenic acid are known for potentially inhibiting arginase, and t...
Source: Medicinal Chemistry Research - July 24, 2023 Category: Chemistry Source Type: research
Discovery of deguelin derivatives in combination with fluconazole against drug-resistant Candida albicans
In this study, a series of deguelin (Deg) derivative were prepared and identified with in vitro antifungal activity against drug-resistantC. albicans combined with fluconazole (FLC). The combination of Deg derivative17c and FLC exhibited the best activity, with a fractional inhibitory combination index (FICI) of 0.02. The sensitization effect of17c + FLC was further validated by the temporal fungicidal curve analysis. In addition,17c + FLC also demonstrated inhibitory effects on the mycelial transformation and biofilm formation of resistantC. albicans, and significantly reduced the expression of key genes related t...
Source: Medicinal Chemistry Research - July 24, 2023 Category: Chemistry Source Type: research
Using molecular networking and docking to explore arginase inhibitors among Drimys brasiliensis chemical constituents
This study has investigated whether the bark and leaves ofDrimys brasiliensis Miers (Winteraceae), a plant known for its antileishmanial effect, can inhibitLeishmania amazonensis arginase. IC50 values of 13.6 and 8.0 μg/mL were obtained for the ethanolic extracts fromD. brasiliensis bark and leaves, respectively. Liquid chromatography –high resolution mass spectrometry analysis of the bioactive extracts helped to identify ten compounds, including flavonoids, phenolic acids, and hydroxycinnamic acid derivatives. Among these compounds, flavonoids and chlorogenic acid are known for potentially inhibiting arginase, and t...
Source: Medicinal Chemistry Research - July 24, 2023 Category: Chemistry Source Type: research
Discovery of deguelin derivatives in combination with fluconazole against drug-resistant Candida albicans
In this study, a series of deguelin (Deg) derivative were prepared and identified with in vitro antifungal activity against drug-resistantC. albicans combined with fluconazole (FLC). The combination of Deg derivative17c and FLC exhibited the best activity, with a fractional inhibitory combination index (FICI) of 0.02. The sensitization effect of17c + FLC was further validated by the temporal fungicidal curve analysis. In addition,17c + FLC also demonstrated inhibitory effects on the mycelial transformation and biofilm formation of resistantC. albicans, and significantly reduced the expression of key genes related t...
Source: Medicinal Chemistry Research - July 24, 2023 Category: Chemistry Source Type: research
Direct syntheses of stereoisomers of 3-fluoro GABA and β-fluoroamine analogues of the calcium receptor (CaR) agonists, cinacalcet, tecalcet, fendiline and NPS R-467
AbstractSynthetic routes following a sequential MacMillan organocatalytic asymmetric α-fluorination protocol for aldehydes and then reductive amination, have allowed ready access to bioactive β-fluoroamines. The approach is demonstrated with a short synthesis of (S)-3-fluoro- γ-aminobutyric acid (3F-GABA) and was extended to β-fluoroamine stereoisomers of cinacalcet, tecalcet, fendiline and NPS R-467, all allosteric modulators of the calcium receptor (CaR). Stereoisomers of the fluorinated calcimimetic analogues were then assayed in a CaR receptor assay and a compariso n of β-fluoroamine matched pair stereoisomers rev...
Source: Medicinal Chemistry Research - July 24, 2023 Category: Chemistry Source Type: research
Lead change of a HIF-2 α antagonist guided by multiparameter optimization and utilization of an Olp→π*Ar interaction
AbstractPharmacokinetic properties of our first-generation HIF-2 α antagonist PT2385, including modest solubility, resulted in a high recommended phase 2 dose (RP2D) of 800 mg BID and motivated the pursuit of novel scaffolds which could improve solubility and formulation parameters with the goal of improved pharmacokinetics. Herein we disclose our successful e fforts to identify such HIF-2α antagonists through an optimization strategy characterized by: (1) increasing the fraction of sp3 hybridized carbons (Fsp3), (2) replacing the aromatic portion of the indane core with pyridine heterocycles, and (3) improving a putat...
Source: Medicinal Chemistry Research - July 18, 2023 Category: Chemistry Source Type: research
A new cadinane sesquiterpenoid from Eupatorium adenophorum and α-glycosidase and AChE inhibitory activities of a gossypetin acylglucoside
AbstractTo investigate the chemical constituents ofEupatorium adenophorum Spreng. (syn. Ageratina adenophora (Spreng.) R.M. King& H. Rob.) growing in Vietnam, the water-soluble fraction from the leaf methanol extract was fractionated by column chromatography. A new sesquiterpenoid, named adenophorone (1), was isolated along with 11 known compounds (2-12). The interpretation of HR-MS and 1D and 2D NMR spectroscopic data together with experimental and theoretical ECD calculations established the absolute stereostructure of compound1. Two isolated flavonol glucosides9 and10 were subjected to enzyme inhibition assays. Goss...
Source: Medicinal Chemistry Research - July 15, 2023 Category: Chemistry Source Type: research
Design, synthesis and antitumor activity evaluation of 2,4,6-trisubstituted quinazoline derivatives containing piperidine moiety
In this study, 35 novel 2,4,6-trisubstituted quinazoline derivatives were designed and synthesized, and their anti-tumor activity in vitro were preliminarily explored. Among them, compound19n exhibited the best anti-proliferative activity against MGC-803 cells with an IC50 of 4.61 μM. Further biological experiments showed that compound19n could inhibit the cloning formation of MGC-803 cells. DAPI staining and apoptosis experiments showed that compound19n could induce apoptosis of MGC-803 cells in a concentration-dependent manner, and the cell cycle experiment indicated that compound19n could also arrest the MGC-803 cel...
Source: Medicinal Chemistry Research - July 15, 2023 Category: Chemistry Source Type: research
A new cadinane sesquiterpenoid from Eupatorium adenophorum and α-glycosidase and AChE inhibitory activities of a gossypetin acylglucoside
AbstractTo investigate the chemical constituents ofEupatorium adenophorum Spreng. (syn. Ageratina adenophora (Spreng.) R.M. King& H. Rob.) growing in Vietnam, the water-soluble fraction from the leaf methanol extract was fractionated by column chromatography. A new sesquiterpenoid, named adenophorone (1), was isolated along with 11 known compounds (2-12). The interpretation of HR-MS and 1D and 2D NMR spectroscopic data together with experimental and theoretical ECD calculations established the absolute stereostructure of compound1. Two isolated flavonol glucosides9 and10 were subjected to enzyme inhibition assays. Goss...
Source: Medicinal Chemistry Research - July 15, 2023 Category: Chemistry Source Type: research
Design, synthesis and antitumor activity evaluation of 2,4,6-trisubstituted quinazoline derivatives containing piperidine moiety
In this study, 35 novel 2,4,6-trisubstituted quinazoline derivatives were designed and synthesized, and their anti-tumor activity in vitro were preliminarily explored. Among them, compound19n exhibited the best anti-proliferative activity against MGC-803 cells with an IC50 of 4.61 μM. Further biological experiments showed that compound19n could inhibit the cloning formation of MGC-803 cells. DAPI staining and apoptosis experiments showed that compound19n could induce apoptosis of MGC-803 cells in a concentration-dependent manner, and the cell cycle experiment indicated that compound19n could also arrest the MGC-803 cel...
Source: Medicinal Chemistry Research - July 15, 2023 Category: Chemistry Source Type: research
Design, synthesis and antitumor activity evaluation of 4,6,7-trisubstituted quinazoline derivatives containing benzothiazole moiety
AbstractA series of novel 4,6,7-trisubstituted quinazoline derivatives containing benzothiazole moiety were designed, synthesized and evaluated for their antitumor activity against four human cancer cells (PC-3, MGC-803, A549 and Eca-109) using MTT assay. Among them, compound11k showed the most potent cytotoxicity against PC-3 cells (IC50 = 5.59 ± 0.78 μM). Compound11k also significantly inhibited the colony formation and migration of PC-3 cells. Meanwhile, compound11k induced cell cycle arrest at S-phase and cell apoptosis, as well as increased accumulation of intracellular reactive oxygen species. All the fin...
Source: Medicinal Chemistry Research - July 13, 2023 Category: Chemistry Source Type: research
Design, synthesis and antitumor activity evaluation of tetrasubstituted pyrimidine derivatives containing methyl phenyl sulfone group
AbstractA series of tetrasubstituted pyrimidine derivatives containing methyl phenyl sulfone structure were designed, synthesized and evaluated for antiproliferative activity against four human cancer cell lines of MGC-803, Eca-109, PC-3 and MCF-7 using methyl thiazolyl tetrazolium (MTT) assay. Most of the compounds displayed moderate to excellent antiproliferative activity against the four human tumor cell lines, among which the compound27g showed the best antiproliferative activity on MGC-803 cells, with IC50 value of (2.98 ± 0.13) μM, which is significantly better than that of the positive control 5-FU. Further s...
Source: Medicinal Chemistry Research - July 12, 2023 Category: Chemistry Source Type: research
