The anti-HIV activity of the phytochemical α-terthienyl

doi:10.1016/0166-3542(93)90057-P

Antiviral Research

Volume 20, Issue 1, January 1993, Pages 33-43

https://doi.org/10.1016/0166-3542(93)90057-P Get rights and content

Abstract

The plant trithiophene, α-terthienyl (αT), was evaluated for activity against the human immunodeficiency virus (HIV-1). Antiviral activity specifically required long wavelength light (UVA, 320–400 nm). The compound had little or no activity in visible light or in the dark. The anti-HIV effect was UVA-dose dependent and was proportional to the concentration of αT, according to several parameters of virus infectivity and replication. The efficacy was decreased to some extent by the presence of bovine serum in the reactions; but under optimal conditions 0.1 μg/ml. αT (3 × 10⁻⁷M) could inactivate 10⁴–10⁵ infectious particles. In contrast poliovirus and Coxsackievirus infectivity were relatively resistant to αT + UVA.

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Cited by (27)

α-Terthienyl induces prostate cancer cell death through inhibiting androgen receptor expression
2022, Biomedicine and Pharmacotherapy
Citation Excerpt :
When α-terthienyl worked as herbicidal substance, transketolase was identified as one of its targets. In the field of medicine, α-terthienyl possessed activity against the human immunodeficiency virus when excited by long wavelength light (UVA, 320–400 nm) [21]. However, its anti-prostate cancer effect is unknown.
Prostate cancer is a disease that often occurs in elderly men. Androgen receptor signaling pathway runs through the occurrence and development of prostate cancer. Thereby, targeting androgen receptor is a crucial strategy for the treatment of prostate cancer. α-Terthienyl, which has been used as photosensitive activator and insecticide, is a natural compound rich in marigold. In the present study, we found α- terthienyl could inhibit the cell viability of four prostate cancer cell lines, especially on LNCaP and 22Rv1 cells which endogenously express androgen receptor. Then we proved that it could inhibit the proliferation of prostate cancer cells and induce apoptosis of prostate cancer cells by plate clone formation assay and flow cytometry respectively. Furthermore, we found α-terthienyl could inhibit androgen receptor nuclear translocation, reduce androgen receptor expression, reduce the mRNA and protein expression of androgen receptor target genes (KLK3, TMPRSS2, PCA3) and nuclear proliferation antigen Ki67 and PCNA. In addition, it inhibited the expression and phosphorylation of Akt protein while increasing the expression of tumor suppressor p27. Besides, we constructed a mouse xenograft prostate cancer model and confirmed that α-terthienyl also inhibited the growth of prostate cancer in vivo. In conclusively, α-terthienyl played an anti-prostate cancer role by inhibiting both the expression of androgen receptor and the transduction of its signal pathway, suggesting that it is a promising natural small molecule for the treatment of prostate cancer.
Plant-microbial interaction: The mechanism and the application of microbial elicitor induced secondary metabolites biosynthesis in medicinal plants
2021, Plant Physiology and Biochemistry
Citation Excerpt :
Thiarubrine A (another elicitor) from the fungi Protomycesgraidus stimulated the production of secondary metabolites from the cell culture of Ambrosia artemisiifolia (Bhagwath and Hjortsø, 2000). These secondary metabolites exhibited stimulates important biological proprieties such as antibiotic and antiviral activities (Towers et al., 1985; Hudson et al, 1986a, 1993). A study by Schnitzler et al. (1992) showed that the inoculation of carrot (Daucus carota) by cells with mycelial homogenate from Pythium aphanidermatum increased the production of p-hydroxybenzoic acid which exhibited antimicrobial (Orjala et al., 1993; Heleno et al., 2013), allelochemical (Huang et al., 2020), immunotherapeutic (Guo et al., 2020), antifeedant (Chandramu et al., 2003), and molluscicidal effects (Orjala et al., 1993).
Plants and microbes interact with each other via different chemical signaling pathways. At the risophere level, the microbes can secrete molecules, called elicitors, which act on their receptors located in plant cells. The so-called elicitor molecules as well as their actions differ according to the mcirobes and induce different bilogical responses in plants such as the synthesis of secondary metabolites. Microbial compounds induced phenotype changes in plants are known as elicitors and signaling pathways which integrate elicitor's signals in plants are called elicitation. In this review, the impact of microbial elicitors on the synthesis and the secretion of secondary metabolites in plants was highlighted. Moreover, biological properties of these bioactive compounds were also highlighted and discussed.
Indeed, several bacteria, fungi, and viruses release elicitors which bind to plant cell receptors and mediate signaling pathways involved in secondary metabolites synthesis. Different phytochemical classes such as terpenoids, phenolic acids and flavonoids were synthesized and/or increased in medicinal plants via the action of microbial elicitors. Moreover, these compounds compounds exhibit numerous biological activities and can therefore be explored in drugs discovery.
Thiophene-derivatized pyridine-biscarboxamide as a sensitizer for Ln<sup>III</sup> luminescence and <sup>1</sup>O<inf>2</inf> generation
2020, Journal of Luminescence
Citation Excerpt :
To better control our ability to generate 1O2 efficiently, without sacrificing the benefit of LnIII luminescence, it is advantageous to expand our knowledge of other 1O2 generating functional groups. Oligohiophene-based compounds, such as 2,2’:5’,2’’-terthiophene, have been studied for their antibiotic [32], insecticidal [33–36], antifungal [37,38], and antiviral [39–41] properties, which occur as a result of the compounds’ ability to generate 1O2. Thiophene and methylthiophene can generate 1O2 as well, as verified by ab initio calculations [42].
Lanthanide ion (Ln^III = Gd^III, Eu^III, Nd^III, Er^III, and Yb^III) complexes of 4-thiophen-3-yl-pyridine-2,6-dicarboxamide (1Tcbx) were isolated and their photophysical properties explored. In acetonitrile, 1Tcbx sensitizes the visible and NIR-emitting Ln^III (Ln^III = Eu^III, Yb^III, Nd^III, and Er^III) ions. Quantum yields of Ln^III sensitization are φ^Eu = 25%, φ^Yb = 0.42%, φ^Nd = 0.19%, and φ^Er = 0.01%. These luminescent complexes generate singlet oxygen (¹O₂) as well, which is monitored through its phosphorescence at 1270 nm. For the Nd^III complex, the formation of ¹O₂ was masked by the intense ⁴F_3/2 → ⁴I_13/2 transition. The efficiency of ¹O₂ generation (φ_1O2) was quantified for [Gd(1Tcbx)₃]³⁺ at 12%.
α-Terthienylmethanol, isolated from Eclipta prostrata, induces apoptosis by generating reactive oxygen species via NADPH oxidase in human endometrial cancer cells
2015, Journal of Ethnopharmacology
Citation Excerpt :
In addition, terthiophenes were reported to have significant anti-viral and cytotoxic activities against murine cytomegalovirus, sindbis virus, and murine mastocytoma cells (Marles et al., 1992). Anti-HIV (Hudson et al., 1993) and inhibitory activities against protein kinase C (Kim et al., 1998) were also suggested. However, the anti-cancer activity and molecular mechanism of the action of terthiophenes are poorly understood in human cancer cells.
Eclipta prostrate L. (syn. E. alba Hassk), commonly known as False Daisy, has been used in traditional medicine in Asia to treat a variety of diseases, including cancer. Although an anti-tumor effect has been suggested for E. prostrata, the exact anti-tumor effects and underlying molecular mechanisms of its bioactive compounds are poorly understood. The aim of this study was to identify compounds with anti-cancer activity from E. prostrata and to investigate their mechanism of action.
To assess cell viability, cell cycle progression, and apoptosis, we performed MTT assays and FACS analysis using Annexin and PI staining. We also investigated reactive oxygen species (ROS) production and caspase activation using flow cytometry and Western blot analysis, respectively. Cytosolic translocation of cytochrome c was measured using an ELISA kit. Antioxidants, MAPK signaling inhibitors, NADPH oxidase inhibitors, and siRNA were used to elucidate the molecular mechanism of action of the compound.
We isolated five terthiophenes from the n-hexane fraction of E. prostrata; of these, α-terthienylmethanol possessed potent cytotoxic activity against human endometrial cancer cells (Hec1A and Ishikawa) (IC₅₀<1 μM). The growth inhibitory effect of α-terthienylmethanol was mediated by the induction of apoptosis, as shown by the accumulation of sub-G1 and apoptotic cells. In addition, α-terthienylmethanol triggered caspase activation and cytochrome c release into the cytosol in a time-dependent manner. Moreover, α-terthienylmethanol increased the intracellular level of ROS and decreased that of GSH, and the antioxidants N-acetyl-l-cysteine and catalase significantly attenuated α-terthienylmethanol-induced apoptosis. We further demonstrated that inhibition of the NADPH oxidase attenuated α-terthienylmethanol-induced cell death and ROS accumulation in endometrial cancer cells.
Overall, these results suggest that α-terthienylmethanol, a naturally occurring terthiophene isolated from E. prostrata, induces apoptosis in human endometrial cancer cells by ROS production, partially via NADPH oxidase.
Photochemical and Photophysical Behavior of Thiophene
2011, Advances in Heterocyclic Chemistry
Citation Excerpt :
Antifeedant activity against larvae of Euxoa messoria was observed: larvae, after a diet containing 100 ppm of a polythiophene derivative in the presence of light decreased the growth rate until death within four weeks (84E577; 84MI104). Polythiophene showed also antiviral and anti-HIV activity (81MI67; 89MI1329; 92PP(56)479; 93MI33; 93PP(58)246; 93MI447; 94MI329; 94PP(60)591). Unfortunately, some phototoxic activity has been found in fishes and some other superior animals (84MI1115; 86MI49; 86MI781; 87MI176).
The photophysical properties and the photochemical behavior of thiophene and thienyl derivatives has been described. Photobiochemical properties of naturally occurrinf thiophenes are reported. The reactivity of thiophene in common reactions such as isomerization, Norrish Type I, dimerization, cycloaddition, arylation, cyclizations, photooxidation, and photopolymerization has been examined. The role of thienyl ring in the synthesis of photochromic substances and in the preparation of optically active material has been discussed. The photochemistry of both thiophene S-oxide or sulphone and dihydrothiophene was examined. The photochemistry of inorganic complexes in the presence of thiophene has been rewieved.
Cytotoxic properties of thiophenes from Echinops grijissi Hance
2008, Phytomedicine
The dichloromethane fraction of the crude ethanol extract of Echinops grijissi Hance roots exhibited different cytotoxicity against a panel of four human tumor cell lines, HepG2, K562, HL60 and MCF-7. By a bioassay-guided fractionation, eight thiophenes were isolated from the dichloromethane fraction, one of them was isolated from the plant for the first time. And they were assayed for their toxicity against the cell lines in order to compare their relative anti-tumor activity and find candidates of potential anti-tumor drugs. The dichloromethane fraction and isolated thiophenes showed different activity against the cell lines, and the anti-tumor activity of the dichloromethane fraction was also studied in vivo in S180 implanted ICR mice, however, it exhibited no anti-tumor activity at dosage of 20 or 40 mg/kg/d. There were also deaths recorded and the animals showed signs of toxicity when the dosage is 200 mg/kg/d.

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Research articleThe anti-HIV activity of the phytochemical α-terthienyl

Abstract

Alternative therapies in HIV infection

AIDS

The plasma distribution of benzoporhyrin derivative and the effects of plasma lipoproteins on its biodistribution

Photochem. Photobiol.

Phototoxins in plant insect interactions

Extracorporeal photopheresis in the treatment of AIDS-related complex: A Pilot Study

Ann. Int. Med.

Photosensitizing action of furocoumarins on membrane components and consequent intracellular events

J. Photochem. Photobiol. B

Light-activated drugs

Sci. Am.

Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy

N. Engl. J. Med.

Photochemistry of the botanical phototoxin, α-terthienyl and some related compounds

Photochem. Photobiol.

Comparison of the phototoxicity of α-terthienyl with that of a selenium and of an oxygen analogue

Photochem. Photobiol.

Psoralen photochemotherapy

J. Am. Acad. Derm.

Plant photosensitizers with antiviral properties

Antiv. Res.

Therapeutic potential of plant photosensitizers

Pharmacol. Ther.

Antiviral activity of photoactive thiophene α-terthienyl

Photochem. Photobiol.

Research article
The anti-HIV activity of the phytochemical α-terthienyl