“…Terpenoids are another group of compounds that undergo enzymatic modifications, and terpenoids such as geraniol, citronellol or essential oils have also been used to obtain flavour compounds (Staudt et al 2020 ). Patil et al ( 2018 ) using Amano lipase AK ( Pseudomonas fluorescens ) synthesized five different compounds via transesterification of vinyl esters with andrographolide, a diterpene and major constituent of Andrographis paniculata with confirmed pharmacological activities. Andrographolide derivatives exhibited higher antibacterial activity than their precursor, and andrographolide-14-propionate (Fig.…”
Section: Application Of Biocatalysis In the Synthesis Of Lipophilic Antioxidants And Antimicrobial Compoundsmentioning
confidence: 99%
“…8 a) and andrographolide-14-butanoate (Fig. 8 b) showed the highest antibacterial activity against E. coli and S. aureus with MIC ranging from 4–8 µg/mL, increased cell membrane permeability and low haemolysis activity (Patil et al 2018 ). Fig.…”
Section: Application Of Biocatalysis In the Synthesis Of Lipophilic Antioxidants And Antimicrobial Compoundsmentioning
Due to the increase in the consumption of highly processed food in developed countries, as well as, a growing number of foodborne diseases, exploration of new food additives is an issue focusing on scientific attention and industrial interest. Functional compounds with lipophilic properties are remarkably desirable due to the high susceptibility to the deterioration of lipid-rich food products. This paper in a comprehensive manner provides the current knowledge about the enzymatic synthesis of lipophilic components that could act as multifunctional food additives. The main goal of enzymatic lipophilization of compounds intentionally added to food is to make these substances soluble in lipids and/or to obtain environmentally friendly surfactants. Moreover, lipase-catalyzed syntheses could result in changes in the antioxidant and antimicrobial activities of phenolic compounds, carbohydrates, amino acids (oligopeptides), and carboxylic acids. The review describes also the implementation of a new trend in green chemistry, where apart from simple and uncomplicated chemical compounds, the modifications of multi-compound mixtures, such as phenolic extracts or essential oils have been carried out.
“…Terpenoids are another group of compounds that undergo enzymatic modifications, and terpenoids such as geraniol, citronellol or essential oils have also been used to obtain flavour compounds (Staudt et al 2020 ). Patil et al ( 2018 ) using Amano lipase AK ( Pseudomonas fluorescens ) synthesized five different compounds via transesterification of vinyl esters with andrographolide, a diterpene and major constituent of Andrographis paniculata with confirmed pharmacological activities. Andrographolide derivatives exhibited higher antibacterial activity than their precursor, and andrographolide-14-propionate (Fig.…”
Section: Application Of Biocatalysis In the Synthesis Of Lipophilic Antioxidants And Antimicrobial Compoundsmentioning
confidence: 99%
“…8 a) and andrographolide-14-butanoate (Fig. 8 b) showed the highest antibacterial activity against E. coli and S. aureus with MIC ranging from 4–8 µg/mL, increased cell membrane permeability and low haemolysis activity (Patil et al 2018 ). Fig.…”
Section: Application Of Biocatalysis In the Synthesis Of Lipophilic Antioxidants And Antimicrobial Compoundsmentioning
Due to the increase in the consumption of highly processed food in developed countries, as well as, a growing number of foodborne diseases, exploration of new food additives is an issue focusing on scientific attention and industrial interest. Functional compounds with lipophilic properties are remarkably desirable due to the high susceptibility to the deterioration of lipid-rich food products. This paper in a comprehensive manner provides the current knowledge about the enzymatic synthesis of lipophilic components that could act as multifunctional food additives. The main goal of enzymatic lipophilization of compounds intentionally added to food is to make these substances soluble in lipids and/or to obtain environmentally friendly surfactants. Moreover, lipase-catalyzed syntheses could result in changes in the antioxidant and antimicrobial activities of phenolic compounds, carbohydrates, amino acids (oligopeptides), and carboxylic acids. The review describes also the implementation of a new trend in green chemistry, where apart from simple and uncomplicated chemical compounds, the modifications of multi-compound mixtures, such as phenolic extracts or essential oils have been carried out.
“…Natural products have been used extensively as traditional medicines for the treatment of various diseases because of their privileged structural diversity. , Andrographolide ( 1 ), one of the bicyclic labdane diterpenoids mainly isolated from the leaves of Andrographis paniculata (AP) Nees (family: Acanthaceae ), is also regarded as a significant natural product having multiple pharmacological properties. The synthetically modified andrographolide ( 1 ) derivatives were also reported for promising biological activities such as antibacterial, antimicrobial, , antihepatotoxic, , anti-HIV, , cardiovascular effects, anticancer, − anti-inflammatory, − antimalarial, antiviral, − antituberculosis, , antidiabetic, − and antioxidant. , Many anticancer mechanisms have been accepted for andrographolide ( 1 ) and its derivatives, including cytotoxicity against cancer cell, apoptosis method, and cell-cycle arrest mechanism. Our group is actively engaged in the development of biologically active natural products and synthetic scaffolds as part of a continuing effort to discover new and more effective anticancer agents. ,− Previous studies of the structure–activity relationships (SARs) of andrographolide have shown that esters on hydroxyl groups present at the C-3, C-19, and C-14 positions enhance pharmacological activities of andrographolide ( 1 ) relevant to its anticancer activity; e.g.…”
A library of 57 compounds
of natural andrographolide was designed,
synthesized, and screened for in vitro studies against
four human cancer cell lines: A594, PC-3, MCF-7, and HCT-116. Most
of the synthesized compounds displayed better cytotoxic profile against
all tested cells compared to the parent andrographolide (1). The tested semisynthetic derivatives of andrographolide were found
to be more sensitive toward lung carcinoma (A594) and prostate carcinoma
(PC-3) cell lines. Among the synthesized compounds, the C-17 p-methoxy phenyl ester analog 8s inhibited
cell proliferation effectively in A549 (IC50: 6.6 μM)
and PC-3 (IC50: 5.9 μM) cell variants, and compound 9s exhibited the most potent activity against the A594 cell
line, with an IC50 value of 3.5 μM. Further anticancer
mechanistic investigation demonstrated that compound 9s displayed nuclear morphological changes and increased reactive oxygen
species (ROS) with disturbed mitochondrial membrane potential (MMP)
that can lead to apoptosis. To know the exact structure confirmation
of intermediate compounds 4 and 5, single
X-ray crystallography was performed, which supported the complete
reaction design of this work.
“…Due to this plant's great therapeutic potential, most related research has been performed on the structural modi cation of andrographolide. This research has mainly included functionalization of the 3, 14, and 19-hydroxyl groups [19][20][21][22][23]; Δ 8,17 double-bond oxidation [24][25][26]; C-15's replacement with the alkylidenyl group [27,28]; Δ 12,13 -alkene isomerization [29]; and the substitution of C-12 with electron-rich groups [30][31][32][33]. In recent years, some novel andrographolide analogs were developed via lactone-bioisosteric versatile catalyst for allylic C-H oxidation which allows for the construction of useful C-O, C-N, and C-C bonds directly from relatively inert allylic C-H bonds.…”
In this paper, using AI78-38, an andrographolide analog with novel skeleton, as the lead compound, we designed and synthesized fteen amide derivatives at the 17 position of AI78-38. In the synthesis of key intermediate IM4, the low yield of the SeO 2 oxidation step impeded the further study. Aiming at improving the yield, White reagent was applied to furnish IM4 by catalyzing the allylic C-H oxidation at the 7, 8, 17 position. It is also rstly reported that White reagent possessed the ability of oxidating the cyclic substrates. Compared with SeO 2 oxidative approach, the modi ed synthetic method utilized by White reagent increased the yield from 32.0% to 53.6%. The anti-in uenza A virus (H3N2) results showed that 4methoxy derivative 10 offered the greatest inhibitory ability, with an IC 50 value of 90.2 mg/ml, slightly more potent than ribavirin. Furthermore, the drug likeness and ADMET properties of compound 10 and AI78-38 were evaluated using the Discovery Studio 2.1 software and the online SwissADME. The results showed that compound 10 offered good bioavailability and overcame the disadvantages of the ADMET properties in , as well as 1, 2-ole nation [38] and terpene ring expansion [39]. These methods have enriched the structural diversity of andrographolide and laid a solid foundation for elucidating the accurate SAR of andrographolide.Although many andrographolide derivatives with various structural characteristics have been successfully synthesized, active analogues with anti-viral activities, especially anti-in uenza virus effects, remain scarce. Most of these analogues belong to the 3, 14, and 19-hydroxyl groups' functional and Δ 12, 13 -alkene isomerized derivatives. Among them, only DASS, AL-1, and DAP have presented de nite antiin uenza viral activities [40,41]. Other compounds showed inhibitory capabilities against Zika, hepatis B, and HIV virus, respectively [26] (Fig. 2). Therefore, it is vital to search for an andrographolide-type antiin uenza viral-active compound with a novel skeleton structure.In previous work, our group successfully semi-synthesized two microbial transformative products, AI78 and AI89, with new structural fragments in which the Δ 8,17 double bond migrated into the ring. Taking AI78 as the lead compound, we synthesized a series of 17-substituted derivatives. Further bioactivity evaluations showed that AI78-38, a 17-benzylamine derivative of AI78, offered the best anti-in uenzavirus H3N2 activity among all derivatives and was superior to the positive control-drug, Lianbizhi (Fig. 3) [42]. This result indicated that this type of substitution at the 17 position can help enhance anti-in uenzavirus effects and suggested that structural optimization at the 17 position in AI78 may offer signi cant advantages in the inhibitory activity of in uenza virus.To further improve the anti-in uenza viral potency of AI78-38, we expanded our research on the reported active compounds. Based on an extensive literature review, we found that the amide group appeared in most active molecules exhibiting ...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
