Podophyllotoxin derivatives: a patent review (2012 – 2014)

Kamal, Ähmed; Hussaini, S.M. Ali; Rahim, Afidah Abdul; Syed, Rabbani

doi:10.1517/13543776.2015.1051727

Cited by 59 publications

(40 citation statements)

References 34 publications

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“…Until recently, the knowledge about its biosynthetic pathway was fragmented and key enzymes and corresponding genes were not known (Kumar et al, 2015). A thorough knowledge of complete biosynthetic pathway would ease the access to podophyllotoxin and its natural derivatives which are difficult to produce synthetically (Kamal et al, 2015). Lau and Sattely (2015) have been able to fill the major gaps in the podophylltoxin biosynthetic pathway with the identification of six new enzymes catalyzing the key steps of podophyllotoxin production (Figure 3).…”

Section: Screening For Bioactive Compoundsmentioning

confidence: 99%

Molecular Approaches to Screen Bioactive Compounds from Endophytic Fungi

2016

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Endophytic fungi are capable of producing plant associated metabolites and their analogs with therapeutic value. In order to identify the potential endophytic isolates producing bioactive compounds, one need to screen all isolated endophytes, which may run into hundreds. Isolation of endophytic fungi is relatively a simple process; but screening of the isolated fungi for required metabolite production is a cumbersome process. Endophytic fungi producing plant associated metabolites may contain genes involved in the entire biosynthetic pathway(s). Therefore, ascertaining the presence of key enzymes of a particular biosynthetic pathway could serve as a molecular marker for screening of these endophytes to produce that metabolite. In absence of entire biosynthetic pathways in endophytic fungi, plant genes associated with that metabolic pathway could serve as markers. This review focuses on the impact of molecular approaches to screen the endophytic fungi for the production of bioactive compounds. An attempt has been made on screening of anticancer compounds like taxol (paclitaxel), podophyllotoxin, and camptothecin using molecular markers. The advantages of molecular approaches over conventional methods to screen endophytic fungi and also identification of endophytic fungi are discussed.

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Section: Screening For Bioactive Compoundsmentioning

confidence: 99%

Molecular Approaches to Screen Bioactive Compounds from Endophytic Fungi

2016

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“…7,8 Similarly, many other modern chemotherapeutic agents have been isolated from plants to treat cancer in clinical situation successfully. [9][10][11][12][13] Recently, scientists and medical professionals have shown increasing interest in this field as they recognize the true health benefits of herbal medicine, which has been playing an important role in the human healthcare since time immemorial.…”

Section: Introductionmentioning

confidence: 99%

Anticancer activity of Helicia nilagirica bedd in mice transplanted with Dalton’s lymphoma

Jagetia¹

2018

IJCAM

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Cancer afflicts everyone and is a dreaded disease as it does not have definite cure, especially for solid tumors in the advanced stages of maligncies. Modern chemotherapeutic regimens are known to induce adverse toxic side effects in the patients undergoing chemotherapy indicating the need to search newer treatment modalities which are less toxic and would cure cancer. The toxic effects of different extracts of Helicia nilagirica were studied by determining the acute toxicity in normal Swiss albino mice, where mice were injected with different doses of the chloroform, ethanol and aqueous extracts of Helicia nilagirica intraperitoneally. The LD50 was found to be 2 g/kg b. wt. for chloroform and 0.75g/kg b. wt. for aqueous extract, whereas the ethanol extract was nontoxic up to a dose of 2g/kg b. wt. The estimation of anticancer activity of Helicia nilagirica in the Dalton's lymphoma tumor bearing mice showed that administration of 50, 75, 100, 125,150 or 175mg/kg b. wt. aqueous extract of Helicia nilagirica resulted in a dose dependent increase in tumor free survival. The highest survival of 16.6% was observed in the mice receiving 175mg/ kg b. wt. aqueous extract, where tumor free survivors were recorded beyond 120 days with an average survival time of 55 and median survival time of 86 days. The administration of different doses of ethanol extract of Helicia nilagirica also elevated the tumor free survival however only up to 38 days for 175mg/kg b. wt. and no tumor free survivors were observed thereafter. The dose of 175mg/kg. b. wt. aqueous extract was chosen for further investigation as maximum tumor free survivors were observed for this dose. The analysis of micronuclei frequency showed a time dependent elevation up to 24h and a decline thereafter. The apoptosis index also increased with assay time up to 36h post treatment. The liver and kidney function tests did not show any significant alteration indicating that it did not exert toxic effect on these two vital organs. Our study demonstrates that Helicia nilagirica is non-toxic and increase the tumor free survival beyond 120 days by inducing DNA damage, apoptosis and necrosis in the tumor cells.Citation: Jagetia GC, Zoremsiami J. Anticancer activity of Helicia nilagirica bedd in mice transplanted with Dalton's lymphoma. Int J Complement Alt Med.Citation: Jagetia GC, Zoremsiami J. Anticancer activity of Helicia nilagirica bedd in mice transplanted with Dalton's lymphoma. Int J Complement Alt Med.

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“…Previous studies have shown that PPT exhibits a wide range of pharmacological properties, including insecticidal, cathartic, antirheumatic, antiviral, and especially antitumor activities (Gordaliza, García, del. Corral, Castro, & Gómez-Zurita, 2004;Kamal, Hussaini, Rahim, & Riyaz, 2015). It shows strong cytotoxic activity against a broad-spectrum of cancer cell lines at the cellular level, and is effective in the treatment of wilms tumors, various genital tumors, non-Hodgkin's lymphomas, and lung cancer (Imbert, 1998;Subrahmanyam et al, 1998;Utsugi et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Click chemistry‐based synthesis and cytotoxic activity evaluation of 4α‐triazole acetate podophyllotoxin derivatives

Hou

Zhang

Luo³

et al. 2018

Chem Biol Drug Des

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A series of novel 4α‐triazole acetate podophyllotoxin derivatives were synthesized via click chemistry. In vitro cytotoxic activity evaluation showed that most of the derivatives exhibited potent inhibitory activities against the tested cancer cell lines with low nanomolar IC50 values. Further studies demonstrated that compound 31 exhibited broad‐spectrum cytotoxic activities, effectively overcame drug‐resistance, and showed relatively weak cytotoxicity on non‐cancer cells. Preliminary mechanistic studies indicated that 31 might have action on microtubule, cause cell cycle arrest at G2/M phase, and induce apoptosis in human PC‐3 cancer cells.

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Podophyllotoxin derivatives: a patent review (2012 – 2014)

Cited by 59 publications

References 34 publications

Molecular Approaches to Screen Bioactive Compounds from Endophytic Fungi

Molecular Approaches to Screen Bioactive Compounds from Endophytic Fungi

Anticancer activity of Helicia nilagirica bedd in mice transplanted with Dalton’s lymphoma

Click chemistry‐based synthesis and cytotoxic activity evaluation of 4α‐triazole acetate podophyllotoxin derivatives

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