Differential induction of Leishmania donovani bi-subunit topoisomerase I–DNA cleavage complex by selected flavones and camptothecin: activity of flavones against camptothecin-resistant topoisomerase I

Emergence of the bi-subunit topoisomerase I in the kinetoplastid family (Trypanosoma and Leishmania) has brought a new twist in topoisomerase research related to evolution, functional conservation and preferential sensitivities to the specific inhibitors of type IB topoisomerase family. In the present study, we describe that naturally occurring flavones baicalein, luteolin and quercetin are potent inhibitors of the recombinant Leishmania donovani topoisomerase I. These compounds bind to the free enzyme and also intercalate into the DNA at a very high concentration (300 µM) without binding to the minor grove. Here, we show that inhibition of topoisomerase I by these flavones is due to stabilization of topoisomerase I–DNA cleavage complexes, which subsequently inhibit the religation step. Their ability to stabilize the covalent topoisomerase I–DNA complex in vitro and in living cells is similar to that of the known topoisomerase I inhibitor camptothecin (CPT). However, in contrast to CPT, baicalein and luteolin failed to inhibit the religation step when the drugs were added to pre-formed enzyme substrate binary complex. This differential mechanism to induce the stabilization of cleavable complex with topoisomerase I and DNA by these selected flavones and CPT led us to investigate the effect of baicalein and luteolin on CPT-resistant mutant enzyme LdTOP1Δ39LS lacking 1–39 amino acids of the large subunit [B. B. Das, N. Sen, S. B. Dasgupta, A. Ganguly and H. K. Majumder (2005) J. Biol. Chem. 280, 16335–16344]. Baicalein and luteolin stabilize duplex oligonucleotide cleavage with LdTOP1Δ39LS. This observation was further supported by the stabilization of in vivo cleavable complex by baicalein and luteolin with highly CPT-resistant L.donovani strain. Taken together, our data suggest that the interacting amino acid residues of topoisomerase I may be partially overlapping or different for flavones and CPT. This study illuminates new properties of the flavones and provide additional insights into the ligand binding properties of L.donovani topoisomerase I

A new friedelane triterpene ester from <i style="mso-bidi-font-style:normal">Pouzolzia indica</i>

1527-1530A new friedelane triterpene ester, 7β-hydroxy-3-oxo-28-dodecyl friedelan-28-oate 1 along with known compounds, friedelin 2, myricyl palmitate 3 and myricylalcohol 4 have been isolated from the dried whole plant of Pouzolzia indica. The structure of the new compound 1 has been established by detailed spectroscopic including 2D NMR experiments and chemical studies

Cornus mas (Linnaeus) Novel Devised Medicinal Preparations: Bactericidal Effect against Staphylococcus aureus and Pseudomonas aeruginosa

The medicinal properties of Cornus mas L. (=Cornus mascula L.), Cornaceae, are well described in Hippocratian documents, and recent research provides experimental evidence for some of these properties. However, the chemical components of Cornus mas L. that may be of pharmaceutical importance are relatively unstable. In this respect a novel methodology for plant nutrient element extraction that provides favorable conditions for simultaneous stabilization of such fragile and unstable structures has been devised. Using this methodology, medicinal preparations derived from Cornus mas L. fresh fruits, proved to possess significant antimicrobial activity selective against S. aureus and P. aeruginosa. This effect became apparent with the addition of sodium bromide in the extraction procedure and varied with the ion availability during extraction. The identification of novel agents with potent antimicrobial activity against these species is of medical importance to overcome the problem of universal antibiotic resistance

19-Epialstonine from <i>Amphicome emodi </i>roots

2698-2700A new indole alkaloid, 19-epialstonine has been isolated from the ethyl acetate extract of the roots of Amphicome emodi. The structure of the alkaloid has been established on the basis of spectroscopic (including 2D NMR experiments) and chemical studies

Anti-SARS-CoV-2, antioxidant and immunomodulatory potential of dietary flavonol quercetin: Focus on molecular targets and clinical efficacy

The current coronavirus disease 2019 (COVID-19) outbreak, caused by the infection of SARS-CoV-2, seems to be a tough global challenge because of its highly contagious nature and rapid evolution of the virus strain. As no effective clinical drugs are available for the treatment of this disease in the early phase till to date, scientists are hunting for drugs from natural sources for its treatment. Quercetin, a dietary polyphenolic flavonoid found in fruits and vegetables, has been reported to exhibit various health-benefit pharmacological properties including antioxidant, anti-inflammatory, antimicrobial, antiviral and anticancer properties. In silico and in vitro studies demonstrated that quercetin potently inhibits the infections of SARS-CoV-2 and other coronaviruses by interfering with viral entry and replication via inhibiting the activity of host ACE2 receptor, and viral S-, 3CL-, PL-, RdRp- and Nsp13 - proteases. Moreover, quercetin is able to suppress oxidative stress, cytokine storm, thrombosis, sepsis and lung fibrosis, and thereby very likely is able to mitigate COVID-19 infection. In this review article, we elaborately discussed the antiviral, immunomodulatory, antioxidant properties of quercetin against viral infections and other diseases, as well as on its nanoformulations for enhancement of oral bioavailability and clinical efficacy in COVID-19 infection for its development as clinical drug for COVID-19

Therapeutic potential of natural alkaloid emetine against emerging COVID-19 and future viral pandemics

The outbreak of COVID-19 pandemic caused by the infection of SARS-CoV-2, has become a global crisis, threatening public health and disrupting global economy. Until now, effective therapeutics against COVID-19 and other coronavirus diseases are in high demand. Several antiviral strategies of drug discovery have identified many small molecules with potent anti-COVID-19 activity. Emetine, one of the main alkaloids of Carapichea ipecacuanha, has been found to exhibit potent antiviral activity against SARS-CoV-2, and other human coronaviruses, multiple RNA and DNA viruses at low nanomolar concentrations in different cell lines. In silico analysis reveals that emetine directly disrupts the activities of SARS-CoV-2 S-protein with host ACE2, and of RdRp-, 3CL-, PL-,and N- proteins. Moreover, emetine shows potent anti-inflammatory and anti-pulmonary arterial hypertensive properties by down-regulating the p38, ERK1/2, NF-κB and RhoA/Rho-kinase/CyPA/Bsg signaling pathways. At low doses, emetine is effective for treatment of COVID-19 patients and other viral infections in rodents. This review discusses the current findings on the antiviral efficacy of emetine against the emerging SARS-CoV-2 and other corona, RNA and DNA viruses, as well as its immunoregulatory pathways and clinical potential in COVID-19 infection for its development as antiviral prodrugs to treat current COVID-19 and future viral pandemics

<span style="font-size:10.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-bidi-font-family: Mangal;mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language: HI" lang="EN-US">Antioxidant flavone glycosides and other constituents from <i style="mso-bidi-font-style:normal">Premna latifolia</i> leaves</span>

746-749A new flavone glycoside, apigenin 7-O---apiofuranosyl (12)---rhamnopyranoside 1 along with known compounds, apigenin 7-O---glucopyranoside-4'-acetate 2 and -sitosterol-3-O---glucoside 3 have been isolated from the MeOH extract of the leaves of the medicinal plant, <i style="mso-bidi-font-style: normal">Premna latifolia Roxb (Verbenaceae)<i style="mso-bidi-font-style: normal">. The structure of the new compound <b style="mso-bidi-font-weight: normal">1 has been elucidated on the basis of detailed spectral (including 2D-NMR) and chemical (including transformations into hexa and hepta acetates) studies. The notations of sugars in 1 have been assigned on GC analysis of their TMS derivatives. The isolation of compound 2 is being reported for the first time from a higher plant. Both flavones 1 and 2 exhibit significant DPPH radical scavenging activity with IC50 value of 16.0 and 22.5 μg/mL, respectively, which is comparable to that of standard antioxidant, BHT (IC50 of 17.5 μg/mL). Hence, the MeOH extract of the leaves of this plant may be useful as a potential source of natural antioxidant. </span

<span style="font-size:10.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-bidi-font-family: Mangal;mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language: HI" lang="EN-US">Flavones and triterpenes from the leaves of <i style="mso-bidi-font-style: normal">Vitex peduncularis</i></span>

279-282A new flavone, 4'-acetoxy-5-hydroxy-6,7-dimethoxyflavone 1 together with four known compounds, cirsimaritin <b style="mso-bidi-font-weight: normal">2, genkwanin 3, 3α-friedelinol <b style="mso-bidi-font-weight: normal">4 and 3β-friedelinol 5 have been isolated from the leaves of Vitex peduncularis Wall. (Verbenaceae). The structure of the new flavone was elucidated by detailed spectral (including 2D-NMR) and chemical studies. </span

Phytochemical investigation of <i>Gomphrena globosa </i>aerial parts

2223-2227One new triterpenoid saponin (gomphrenoside,1) and one new hopane derivative (hopan-7β-ol,2) along with known compounds, β-sitosterol-β-D-glucoside and 1-triacontanol have been isolated from the aerial parts of Gompizrena globosa. On the basis of chemical and spectroscopic(including 20 NMR) methods, the structure of 1 has been elucidated as 3β-O-α-L- arabinopyranosyl-6β-hydroxyolean-12-ene-23,29-dioic acid-29-O-β-D-glucopyranoside and structure of 2 is determined

Chemical constituents of Evolvulus nummularius

492-498Three new compounds, 1-3 together with known compounds, β-sitosterol and its glucoside, stigmasterol, d-mannitol, ursolic acid and oleanolic acid have been isolated from the aerial parts of Evolvulus nummularius. On the basis of their spectroscopic data and chemical study, the structures of the new compounds 1-3 have been established as 3-O-(4-stearoyl-Z-coumaroyl)-stigmast-5, E–22–dien-3β-ol; 16-(E-coumaroyloxy)-palmitic acid and 3β-hydroxy-urs-12-en-29β-oic acid, respectively. Possibly compound 3 is identical with plectranthoic acid, whose structure was wrongly assigned as 3α-hydroxy-urs-12-en-29β-oic acid