In-vitro and in-silico evaluations of heterocyclic-containing diarylpentanoids as Bcl-2 inhibitors against LoVo colorectal cancer cells

In the present study, we investigated the in-vitro anti-cancer potential of six diarylpentanoids against a panel of BRAF- and KRAS-mutated colorectal cancer cell lines including T84, SW620, LoVo, HT29, NCI-H508, RKO, and LS411N cells. Structure-activity relationship study suggested that the insertions of tetrahydro-4H-thiopyran-4-one and brominated phenyl moieties are essential for better cytotoxicity. Among the evaluated analogs, 2e has been identified as the lead compound due to its low IC50 values of approximately 1 µM across all cancer cell lines and high chemotherapeutic index of 7.1. Anti-proliferative studies on LoVo cells showed that 2e could inhibit cell proliferation and colony formations by inducing G2/M cell cycle arrest. Subsequent cell apoptosis assay confirmed that 2e is a Bcl-2 inhibitor that could induce intrinsic cell apoptosis by creating a cellular redox imbalance through its direct inhibition on the Bcl-2 protein. Further molecular docking studies revealed that the bromophenyl moieties of 2e could interact with the Bcl-2 surface pocket through hydrophobic interaction, while the tetrahydro-4H-thiopyran-4-one fragment could form additional Pi-sulfur and Pi-alkyl interactions in the same binding site. In all, the present results suggest that 2e could be a potent lead that deserves further modification and investigation in the development of a new Bcl-2 inhibitor

In vitro and in silico evaluations of diarylpentanoid series as a-glucosidase inhibitor

A series of thirty-four diarylpentanoids derivatives were synthesized and evaluated for their α-glucosidase inhibitory activity. Eleven compounds (19, 20, 21, 24, 27, 28, 29, 31, 32, 33 and 34) were found to significantly inhibit α-glucosidase in which compounds 28, 31 and 32 demonstrated the highest activity with IC50 values ranging from 14.1 to 15.1 µM. Structure-activity comparison shows that multiple hydroxy groups are essential for α-glucosidase inhibitory activity. Meanwhile, 3,4-dihydroxyphenyl and furanyl moieties were found to be crucial in improving α-glucosidase inhibition. Molecular docking analyses further confirmed the critical role of both 3,4-dihydroxyphenyl and furanyl moieties as they bound to α-glucosidase active site in different mode. Overall result suggests that diarylpentanoids with both five membered heterocyclic ring and polyhydroxyphenyl moiety could be a new lead design in the search of novel α-glucosidase inhibitor

Comparative study of the antioxidant activities of some lipase-catayzed alkyl dihydrocaffeates synthesized in ionic liquid

The solubility limitations of phenolic acids in many lipidic environments are now greatly improved by their enzymatic esterification in ionic liquids (ILs). Herein, four different ILs were tested for the esterification of dihydrocaffeic acid with hexanol and the best IL was selected for the synthesis of four other n-alkyl esters with different chain-lengths. The effect of alkyl chain length on the anti-oxidative properties of the resulted purified esters was investigated using β-carotene bleaching (BCB) and free radical scavenging method DPPH and compared with butylated hydroxytoluene (BHT) as reference compound. All four esters (methyl, hexyl, dodecyl and octadecyl dihydrocaffeates) exhibited relatively strong radical scavenging abilities. The scavenging activity of the test compounds was in the following order: methyl ester>hexyl ester⩾dodecyl ester>octadecyl ester>BHT while the order for the BCB anti-oxidative activity was; BHT>octadecyl ester>dodecyl ester>hexyl ester>methyl ester

Antinociceptive activity of 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol in mice

A novel compound from diarylpentanoids analogues, 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol, was evaluated on its antinociceptive activity in mice through acetic acid-induced abdominal constriction test. Antinociception of 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol was indicated by the reduction in the mean of the number of abdominal constrictions in the test groups compared to the control group. Acetylsalicylic acid (ASA, 100 mg/kg) was used as reference drugs while control group only received vehicle (5% DMSO: 5% Tween 20: 90% Distilled water) that used to dissolve the compound. The mice that received intraperitoneal injections of 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol at 0.1, 0.3, 1.0 and 3.0 mg/kg showed 48.34%, 60.79%, 90.07% and 98.54% of inhibition respectively. Acetic acid injection in mice peritoneal cavity can promote the release of many inflammatory mediators such as prostaglandin, bradykinin, substance P, TNF-α, IL-1β, IL-8 and other mediator, which will then stimulate primary afferent neurons to enhance the release of aspartate and glutamate. Hence, the result obtained from this chemical model of nociception suggests that the antinociceptive activity of 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol may be linked partly to the inhibition of the inflammatory mediators

α‐Glucosidase inhibitory and antioxidant activities of different ipomoea aquatica cultivars and LC–MS/MS profiling of the active cultivar

The present study was designed to investigate the effect of Ipomoea aquatica extracted using water and methanol at various concentrations on the total phenolics, antioxidant capacity, and a-glucosidase inhibitory activities. Three I. aquatica cultivars were used in this study including the upland type with narrow leaves (K-11), low-land aquatic types with broader shaped leaves (K-25), and bamboo-shaped leaves (K-88). The results revealed that 70% methanol extract of K-11 showed higher total phenolic content and a-glucosidase inhibitory and antioxidant activities than the other two cultivars. The phytochemical constituents in the active extract K-11 were analyzed by means of liquid chromatography coupled with diode array detection and electrospray tandem mass spectroscopy. Eighteen compounds were detected of which 13 were tentatively identified as quercetin-3-O-sophoroside, quercetin-3-O-glucoside, quercetin-3,7-di-O-glucoside, nomilinic acid glucoside, 4,5-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, luteolin-7-glucoside and 3,4,5-tricaffeolquinic acid, fatty acid together with quercetin, and tricaffeoylquinic acid derivatives

Chemical constituents and biological activities of South East Asia marine sponges: a review

The ocean has an exceptional resource with various groups of natural products that are potentially useful for biomedical and other applications. Marine sponges have prominent characteristic natural products with high diversity. They produce many vital therapeutic metabolites with prominent biological activities. Marine invertebrates and microbial communities are the primary producers of such metabolites. Among the richest sources of these metabolites, class Demospongiae and the order Haplosclerida and genus Xestopongiae from family Petrosiidae are of interest. This review summarizes the research that has been conducted on two classes, eight orders, twelve families and fourteen genera of marine sponges available in the South East Asia region, covering the literature of the last 20 years. Ninety-five metabolites including alkaloids, sterols, terpenoids, quinones isolated from marine sponges collected in South East Asia along with their bioactivities especially cytotoxicity and antibacterial activities were reported in this review. Chemistry and biology are highly involved in studying marine sponges. Thus, tight collaboration is needed for understanding their taxonomy aspects. This review will outline chemistry and biological aspects, challenge, limitation, new idea and a clear future perspective on the discovery of new drugs from South East Asia's marine sponges

Identification of α-glucosidase inhibitory compounds from Curcuma mangga fractions

Curcuma mangga is a medicinal plant, and its rhizomes are often used to treat various conditions, such as fever, thorax pain, itching, stomachaches, skin diseases, gout, and asthma. Although C. mangga is commonly used, information on the relationship between its chemical constituents and the bioactivities of the rhizomes is still limited. The extraction solvents used have a strong effect on the metabolite profile and the bioactivity of the extract. A nuclear magnetic resonance (NMR)-based metabolomics approach was used to differentiate the metabolite profiles of hexane, chloroform, ethyl acetate, and methanol fractions of C. mangga rhizomes and to correlate the metabolites with α-glucosidase inhibitory activity. Primary and secondary metabolites were identified, including curcuminoids, carbohydrates, terpenoids, and amino acids. The ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) analysis of the most active fraction (ethyl acetate) revealed the identification of additional metabolites, such as zerumin A, epigallocatechin, p-hydroxycinnamic, and copallic acids. A partial least square (PLS) biplot demonstrated that the existence of curcumin, demethoxycurcumin, curcumanggoside, calcaratarin A, labda-8(17),12-diene-15,16-dial, zerumin B, and difurocumenonol in the ethyl acetate fraction could be responsible for the α-glucosidase inhibitory activity