Assessment on facile Diels-Alder approach of α-pyrone and terpenoquinone for the expedient synthesis of various natural scaffolds.

The development of highly facile synthetic procedures for the expedient synthesis of complex natural molecules is always in demand. As this aspect, the Diels-Alder reaction (DAR) has a versatile approach to the synthesis of complex natural compounds and highly regio-/stereoselcetive heterocyclic scaffolds. Additionally, α-pyrone and terpenoquinone are two versatile key intermediates that are prevalent in various bioactive natural compounds for instance, (±)-crinine, (±)-joubertinamine, (±)-pancratistatin, (-)-cyclozonarone, and 8-ephipuupehedione, etc. Hence, the current review summarizes the Diels-Alder reaction application of α-pyrone and terpenoquinone to the constructive synthesis of various natural products over the past two decades (2001-2021). Equally, it serves as a stencil for the invention and development of new synthetic strategies for high-complex molecular structured natural and heterocyclic molecules.

Sophora interrupta Bedd. root-derived flavonoids as prominent antiviral agents against Newcastle disease virus.

The discovery and development of novel antiviral drugs from natural sources is continuously increasing due to limitations of currently available drugs such as toxic side effects, drug residue risk factors, high costs, and poor therapeutic strategies. Also, there are very few known antiviral drugs that are effective against only specific viruses. Hence, the present study is intended to isolate and characterize potent antiviral compounds from the methanolic root extract of Sophora interrupta Bedd. against avian paramyxovirus, Newcastle disease virus (NDV) and to distinguish the molecular basis of antiviral compounds. The two isolated flavonoids, maackiain (SR-1) and echinoisoflavanone (SR-2) exhibited the best antiviral activities against NDV infection in chicken embryo fibroblast cell lines compared to the standard antiviral drug, Ribavirin. Further, the in vitro studies and quantitative PCR analysis suggests that these flavonoids inhibit the viral entry, replication, and transcription, which may be beneficial as a promising strategy for the treatment of viral infections. Besides, the molecular docking studies of SR-1 and SR-2 exhibited high binding affinities of -7.6 and -8.0 kcal mol-1, respectively, and marked interactions with the NDV surface glycoprotein, hemagglutinin neuraminidase (HN). Also, the in silico toxicity properties as well pharmacokinetic studies of isolates revealed them as pharmacologically potent antiviral compounds.

Phytochemistry and pharmacological activities of the genus Rhynchosia: a comprehensive review.

MAIN CONCLUSION: The genus Rhynchosia is a rich source of natural compounds especially flavonoids and prenylated isoflavonoids. Further experimental studies on Rhynchosia members may be result new and novel secondary metabolites with potent biological activities. Traditionally, medicinal plants have played a significant role on human life since ancient days. At present, natural compounds are the major source for the modern drug discovery owing to their therapeutic selectivity, minutest of side effects, inexpensive source and serve as lead molecules for the discovery of new drugs. Rhynchosia species (Fabaceae) are extensively circulated throughout the tropical and subtropical areas around the world. A few plants of this genus were used in traditional medicine for the treatment of various ailments such as antibacterial, antidiabetic, abortifacients, healing of wounds, hepatoprotective, remedial of boils, rheumatic pains and skin infections. The present review compiles traditional uses, isolated chemical compounds and pharmacological activities of Rhynchosia species. So far, in total, seventy-seven compounds were isolated from the genus Rhynchosia, including flavonoids, isoflavonoids, flavan-3-ols, xanthones, biphenyls, simple polyphenols and sterols. It is interesting to note that the genus Rhynchosia is a rich source of C-glycosylflavonoids and prenylated isoflavonoids. Further, phytochemical and pharmacological studies on this genus are required since only few species have been investigated so far.

Isolation of flavonoids from the flowers of Rhynchosia beddomei Baker as prominent antimicrobial agents and molecular docking.

Rhynchosia beddomei Baker (R. beddomei) is a viscous hairy under shrub, belongs to the family of Fabaceae and widely distributed in Deccan and Carnatic regions of South India. In the present investigation, four flavonoids such as an isoflavone, 5,7-dihydroxy-4'-methoxyisoflavone (RB-1), a flavonol, quercetin-7-O-methylether (RB-2), two flavone C-glycosides, isovitexin (RB-3) and 5,7,3',4'-tetrahydroxy-6-C-ß-d-glucopyranosyl flavone (RB-4) were isolated from the flowers of R. beddomei Baker through bioassay guided fractionation. Subsequently, antimicrobial activity of compounds against drug resistant gram positive and negative bacteria and fungi revealed RB-2 and RB-4 have shown highest minimal inhibition concentrations against Pseudomonas aeruginosa and Candida albicans. RB-2 and RB-4 enclosed OH groups at 5th position on the ring A, 3' and 4' ortho dihydroxyl groups positioned on the ring B and accomplished efficacious antibacterial activity. In addition, Docking studies perceptible that RB-4 conferred highest binding energy of -10.5 kcal/mol and exhibited eloquent polar and non-polar interactions with active site residues of N-Myristoyltransferase (Nmt) of Candida albicans while binding energy of -7.5 kcal/mol was recorded for peptidyldeformylase (PaPDF) of Pseudomonas aeruginosa. Moreover, these compounds obey Lipinski's rule of five and exerts good drug likeness properties and might be ratified as lead molecules for further investigations to prevent panicking microbial infections.

Development of novel HER2 inhibitors against gastric cancer derived from flavonoid source of Syzygium alternifolium through molecular dynamics and pharmacophore-based screening.

Continuous usage of synthetic chemotherapeutic drugs causes adverse effects, which prompted for the development of alternative therapeutics for gastric cancer from natural source. This study was carried out with a specific aim to screen gastroprotective compounds from the fruits of Syzygium alternifolium (Myrtaceae). Three flavonoids, namely, 1) 5-hydroxy-7,4'-dimethoxy-6,8-di-C-methylflavone, 2) kaempferol-3-O-ß-d-glucopyranoside, and 3) kaempferol-3-O-α-l-rhamnopyranoside were isolated from the above medicinal plant by employing silica gel column chromatography and are characterized by NMR techniques. Antigastric cancer activity of these flavonoids was examined on AGS cell lines followed by cell cycle progression assay. In addition, pharmacophore-based screening and molecular dynamics of protein-ligand complex were carried out to identify potent scaffolds. The results showed that compounds 2 and 3 exhibited significant cytotoxic effect, whereas compound 1 showed moderate effect on AGS cells by inhibiting G2/M phase of cell cycle. Molecular docking analysis revealed that compound 2 has higher binding energies on human growth factor receptor-2 (HER2). The constructed pharmacophore models reveal that the compounds have more number of H-bond Acc/Don features which contribute to the inhibition of HER2 activity. By selecting these features, 34 hits were retrieved using the query compound 2. Molecular dynamic simulations (MDS) of protein-ligand complexes demonstrated conspicuous inhibition of HER2 as evidenced by dynamic trajectory analysis. Based on these results, the compound ZINC67903192 was identified as promising HER2 inhibitor against gastric cancer. The present work provides a basis for the discovery a new class of scaffolds from natural products for gastric carcinoma.

A New Geranylated Chalcone from Andrographis lobelioides.

A new O-geranylated chalcone, 2'-hydroxy-2-methoxy-4'-O-[(E)-3,7-dimethyl-2,6-octadienyl] chalcone (1), together with three known flavones, 5-hydroxy-7,2'-dimethoxyflavone (2), skullcapflavone I (3) and echioidin (4), were isolated from the leaves of Andrographis lobelioides. The structure of 1 and the known compounds (2-4) were achieved by extensive 1D and 2D NMR spectral and chemical studies.

Isoorientin, a Selective Inhibitor of Cyclooxygenase-2 (COX-2) from the Tubers of Pueraria tuberosa.

Bioassay-guided fraction of the methanol extract of the roots of Pueraria tuberose DC yielded puerarin, an isoflavone C-glycoside (PT-1), isoorientin, a flavone C-glycoside (PT-2) and mangiferin, a xanthone C-glycoside (PT-3). The extracts and the isolated compounds were screened for potent anti-inflammatory components inhibiting the cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX), the target enzymes of inflammation, by employing spectroscopic/polorographic methods. Among these, isoorientin was found to be a potent inhibitor of COX-2with an IC50 value of 39 µM. Docking studies were carried out to understand the interactions of isorientin (PT-2) with COX-2.The structures of the isolates were determined by mass spectrometry and 2D-NMR techniques including HSQC, HMBC, NOESY and 1H-1H COSY experiments. Although isoorientin and mangiferin have been reported from several plant sources, this is the first report of their isolation from a Pueraria species.

Structure elucidation and antioxidant activity of the phenolic compounds from Rhynchosia suaveolens.

A new benzophenone, 2-hydroxy-3,4-dimethoxybenzophenone (1), together with a known C-glycosylxanthone, mangiferin (2) and two known C-glycosylflavones, isovitexin (3) and isoorientin (4), were isolated from the flowers of Rhynchosia suaveolens DC. (Fabaceae). The structure of the new compound (1) and the known compounds (2-4) were elucidated by extensive 1D and 2D NMR spectral studies. The plant extracts, as well as the isolated compounds, were evaluated for their total phenolic content (TPC), total flavonoid content (TFC) and DPPH radical scavenging activity. Among the isolated compounds, mangiferin (2) and isoorientin (4) showed significant radical scavenging activity comparable with that of ascorbic acid.

A new di-C-prenylated coumarin from Sophora interrupta.

A new di-C-prenylated coumarin, 7-methoxy-6,8-bis-(2,3-dihydroxy-3-methylbutyl)-coumarin (1), together with seven known compounds, isopimpinellin (2), an arylbenzofuran (3), three flavonoids (4-6), (+)-maackianin (7) and echinoisoflavanone (8), were isolated from the leaves of Sophora interrupta Bedd. The structure of the new compound 1 as well as known compounds was elucidated by extensive 1D and 2D NMR spectral studies.

Two new chalcones from Clerodendrum phlomidis.

Two new chalcones, 3,2',3'-trihydroxy-4'-methoxychalcone (1) and 3,2'-dihydroxy-4',6'-dimethoxychalcone (2), were isolated from the seeds of Clerodendrum phlomidis together with three known flavonoids, 5-hydroxy-7-methoxyflavanone (3), 5-hydroxy-7-methoxyflavone (4), and kaempferol-3-O-α-l-rhamnopyranoside (5). The structures of the new compounds 1 and 2 have been established mainly on the basis of 1D and 2D NMR studies.

Two new chalcones from the flowers of Clerodendrum inerme.

Two new chalcones, 3-hydroxy-3',4'-dimethoxychalcone (1) and 3,2'-dihydroxy-3',4'-dimethoxychalcone (2), were isolated from the flowers of Clerodendrum inerme (L.) Gaertn together with two known flavones, 7-O-methylwogonin (3) and eucalyptin (4). The structures of the new compounds 1 and 2 have been established by extensive 2D-NMR and ESI-TOFMS studies.

A new O-prenylated flavonol from the roots of Sophora interrupta.

A new O-prenylated flavonol, 3',4'-dimethoxy-7-(γ,γ-dimethylallyloxy)flavonol (1), together with three known compounds, 2'-hydroxy-3,4-dimethoxychalcone (2), biochanin A (3) and kaempferol-3-O-ß-D-glucopyranoside (4), were isolated from the roots of Sophora interrupta Bedd. The structure of compound 1 was elucidated by extensive 1D and 2D NMR spectral studies.

Two new flavonoids from the seeds of Derris scandens.

Two new flavonoids, (2S)-3',4',5'-trimethoxyflavanone (1) and 2'-hydroxy-2,4-dimethoxy-4'-O-[(E)-3,7-dimethyl-2,6-octadienyl]chalcone (2), together with a known pterocarpene, flemichapparin B (3), and a known rotenoid, dehydrodeguelin (4), were isolated from the seeds of Derris scandens. Their structures were determined by means of extensive 1D and 2D NMR spectral studies.

Phytochemical and biological studies of Ochna species.

The genus Ochna L. (Gr, Ochne; wild pear), belonging to the Ochnaceae family, includes ca. 85 species of evergreen trees, shrubs, and shrublets, distributed in tropical Asia, Africa, and America. Several members of this genus have long been used in folk medicine for treatment of various ailments, such as asthma, dysentery, epilepsy, gastric disorders, menstrual complaints, lumbago, ulcers, as an abortifacient, and as antidote against snake bites. Up to now, ca. 111 constituents, viz. flavonoids (including bi-, tri-, and pentaflavonoids), anthranoids, triterpenes, steroids, fatty acids, and a few others have been identified in the genus. Crude extracts and isolated compounds have been found to exhibit analgesic, anti-HIV-1, anti-inflammatory, antimalarial, antimicrobial, and cytotoxic activities, lending support to the rationale behind several of its traditional uses. The present review compiles the informations concerning the traditional uses, phytochemistry, and biological activities of Ochna.

A new diacylated labdane diterpenoid from Andrographis wightiana.

A new acylated labdane diterpenoid, 14-deoxy-3,19-diacetyl-11,12-didehydroandrographolide (1), together with three known labdane diterpenoids, wightionolide (2), andrographolide (3) and neoandrographolide (4), and three known flavones, echioidinin (5), skullcapflavone I 2'-methyl ether (6) and echioidin (7), were isolated from the whole plant of Andrographis wightiana. The structure of compound 1 was elucidated by 1D and extensive 2D-NMR spectral studies.

Flavonoids from Tephrosia calophylla.

Two new flavanones, (2S)-5-hydroxy-7,4'-di-O-(gamma,gamma-dimethylallyl)flavanone (1) and 6-hydroxy-E-3-(2,5-dimethoxybenzylidine)-2',5'-dimethoxyflavanone (2), together with three known compounds, tephrowatsin C, afrormosin and kaempferol 3-O-beta-D-glucopyranoside were isolated from the roots of Tephrosia calophylla. The structures of 1 and 2 were established by extensive 2D NMR spectral studies.

A new acylated flavone glycoside from Colebrookea oppositifolia.

A new acylated flavone glycoside, echioidinin 2'-O-beta-D-(2''-O-acetyl)glucopyranoside (1) along with the three known flavonoids, 5,6,7,8,5'-pentamethoxy-3',4'-methylenedioxyflavone (2), 5,2',6'-trihydroxy-7-methoxyflavone (3), and kaempferol 7,4'-dimethyl ether 3-O-beta-D-glucopyranoside (4), were isolated from the roots of Colebrookea oppositifolia. The structure of compound 1 was elucidated by extensive spectral and chemical studies.

A new di-O-prenylated isoflavone from Tephrosia tinctoria.

A new di-O-prenylated isoflavone, 5,7-di-O-prenylbiochanin A (1), together with three known compounds, 7-O-methylglabranin (2), tephrowatsin C (3) and flemichapparin B (4), were isolated from the stems of Tephrosia tinctoria. The structures of these compounds were elucidated by extensive 2D NMR spectral studies.

Flavonoids from Limnophila indica.

Two flavonoids, (2S)-5,7,3',4'-tetramethoxyflavanone (1) and 5,7,2',5'-tetramethoxyflavone (2) together with three known flavonoids, 7-O-methylwogonin (3), skullcapflavone I (4) and 5-hydroxy-7,2'-dimethoxyflavone (5) were isolated from the whole plant of Limnophila indica. The structures of compounds 1-5 were elucidated on the basis of spectral and chemical studies.

A flavanone and a dihydrodibenzoxepin from Bauhinia variegata.

Phytochemical analysis of the root bark of Bauhinia variegata Linn yielded a new flavanone, (2S)-5,7-dimethoxy-3',4'-methylenedioxyflavanone (1) and a new dihydrodibenzoxepin, 5,6-dihydro-1,7-dihydroxy-3,4-dimethoxy-2-methyldibenz [b,f]oxepin (2) together with three known flavonoids (3-5). The structures of the new compounds were determined on the basis of spectral studies.