Assignments got your hair on fire?

Douse the flames with our full-range writing service!

Experienced academic writing professionals are at your fingertips. Use this handy tool to get a price estimate for your project.

Synthesis of (-)-Podophyllotoxin - Organic chemistry

A series of novel spin-labeled 4β-[(4-substituted)-1,2,3-triazol-1-yl]podophyllotoxin derivatives (17a-h) were firstly designed and synthesized with significant regioselectivity by employing Cu(I) catalyzed click approach, and evaluated for cytotoxicity against four human tumor cell lines (A-549, DU145, KB, and KBvin). Among them, compound 17h displayed the highest cytotoxic activity against the tumor cell lines tested. Significantly, compound 17h showed superior cytotoxic activity compared with etoposide (IC50 6.30 to >10 μM), a clinically available anticancer drug. Significant activity toward the drug resistant KBvin cell line revealed promising future for compound 17h as a new generation of epipodophyllotoxin-derived antitumor clinical trial candidate.

Podophyllotoxin is the starting material for the semi-synthesis of the anti-cancer drugs etoposide, teniposide and etopophos. These compounds have been used for the treatment of lung and testicular cancers as well as certain leukemias. It is also the precursor to a new derivative CPH 82 that is being tested for rheumatoid arthritis in Europe, and it is the precursor to other derivatives used for the treatment of psoriasis and malaria. Several podophyllotoxin preparations are on the market for dermatological use to treat genital warts. Since the total synthesis of podophyllotoxin is an expensive process, availability of the compound from natural renewable resources is an important issue for pharmaceutical companies that manufacture these drugs.

ring e-modified analogues of (-)-podophyllotoxin and etoposide and a method for their synthesis
Photo provided by Pexels

Podophyllotoxin (PPT), also known as podofilox, ..

Several strategies have emerged to design and synthesize analogs of etoposide or podophyllotoxin with improved pharmaceutical ..
Photo provided by Flickr

AB - These studies explore the effects of an epipodophyllotoxin on the membrane transport and metabolism of thymidine in Ehrlich ascites tumor cells. Uptake of 3H after exposure of cells to [3H]thymidine is characterized by a rapid initial velocity that approximates membrane transport followed by a slower rate of uptake that parallels the accumulation of phosphorylated derivatives of thymidine, primarily thymidine triphosphate, within the cell. The high rate of thymidine transport relative to thymidine metabolism to the triphosphate within the cell decreases as the extracellular nucleoside concentration is reduced due to a much greater decrease in membrane transport than the subsequent metabolic step. Hence, as extracellular thymidine is decreased, transport becomes increasingly rate limiting to metabolism within the cell. VP-16-213 (etoposide) or podophyllotoxin inhibits the initial uptake rate for thymidine and, as a consequence, inhibits the intracellular formation of thymidine triphosphate. When extracellular thymidine is high, inhibitory effects on transport are transient, and the net rate of thymidine triphosphate accumulation within drug-treated cells rapidly approaches a velocity comparable to that of control cells, indicating no direct VP-16-213 or podophyllotoxin effect on nucleoside and nucleotide phosphorylation. When extracellular thymidine is reduced so that transport is rate limiting to metabolism, the duration of the inhibitory effects of VP-16-213 on thymidine triphosphate formation is prolonged. A secondary effect of VP-16-213 becomes manifest beyond 10 min of incubation with [3H]thymidine with the virtual complete cessation of thymidine incorporation into the acid precipitate without any change in the thymidine triphosphate level. This late effect is not observed with podophyllotoxin and indicates a direct effect of VP-16-213 on DNA synthesis that is distinct from the earlier inhibitory effect on thymidine phosphorylation, which is secondary to membrane transport.

Researchers at the G.B. Pant Institute of Himalayan Environment and Development in Garhwal have approached the replenishing of by propagating the natural stocks using rhizome cuttings, viable seeds, and plants regenerated from embryogenic calli (Nadeem et al. 2000). Researchers at the National Center for Natural Products Research (NCNPR) are also attempting to secure podophyllotoxin supply by developing the American mayapple into an alternative source.

ABSTRACT The synthesis of the glycosyl donors 2,3-di-O ..

N2 - These studies explore the effects of an epipodophyllotoxin on the membrane transport and metabolism of thymidine in Ehrlich ascites tumor cells. Uptake of 3H after exposure of cells to [3H]thymidine is characterized by a rapid initial velocity that approximates membrane transport followed by a slower rate of uptake that parallels the accumulation of phosphorylated derivatives of thymidine, primarily thymidine triphosphate, within the cell. The high rate of thymidine transport relative to thymidine metabolism to the triphosphate within the cell decreases as the extracellular nucleoside concentration is reduced due to a much greater decrease in membrane transport than the subsequent metabolic step. Hence, as extracellular thymidine is decreased, transport becomes increasingly rate limiting to metabolism within the cell. VP-16-213 (etoposide) or podophyllotoxin inhibits the initial uptake rate for thymidine and, as a consequence, inhibits the intracellular formation of thymidine triphosphate. When extracellular thymidine is high, inhibitory effects on transport are transient, and the net rate of thymidine triphosphate accumulation within drug-treated cells rapidly approaches a velocity comparable to that of control cells, indicating no direct VP-16-213 or podophyllotoxin effect on nucleoside and nucleotide phosphorylation. When extracellular thymidine is reduced so that transport is rate limiting to metabolism, the duration of the inhibitory effects of VP-16-213 on thymidine triphosphate formation is prolonged. A secondary effect of VP-16-213 becomes manifest beyond 10 min of incubation with [3H]thymidine with the virtual complete cessation of thymidine incorporation into the acid precipitate without any change in the thymidine triphosphate level. This late effect is not observed with podophyllotoxin and indicates a direct effect of VP-16-213 on DNA synthesis that is distinct from the earlier inhibitory effect on thymidine phosphorylation, which is secondary to membrane transport.

A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA.
Photo provided by Pexels

These studies explore the effects of an epipodophyllotoxin on the membrane transport and metabolism of thymidine in Ehrlich ascites tumor cells. Uptake of 3H after exposure of cells to [3H]thymidine is characterized by a rapid initial velocity that approximates membrane transport followed by a slower rate of uptake that parallels the accumulation of phosphorylated derivatives of thymidine, primarily thymidine triphosphate, within the cell. The high rate of thymidine transport relative to thymidine metabolism to the triphosphate within the cell decreases as the extracellular nucleoside concentration is reduced due to a much greater decrease in membrane transport than the subsequent metabolic step. Hence, as extracellular thymidine is decreased, transport becomes increasingly rate limiting to metabolism within the cell. VP-16-213 (etoposide) or podophyllotoxin inhibits the initial uptake rate for thymidine and, as a consequence, inhibits the intracellular formation of thymidine triphosphate. When extracellular thymidine is high, inhibitory effects on transport are transient, and the net rate of thymidine triphosphate accumulation within drug-treated cells rapidly approaches a velocity comparable to that of control cells, indicating no direct VP-16-213 or podophyllotoxin effect on nucleoside and nucleotide phosphorylation. When extracellular thymidine is reduced so that transport is rate limiting to metabolism, the duration of the inhibitory effects of VP-16-213 on thymidine triphosphate formation is prolonged. A secondary effect of VP-16-213 becomes manifest beyond 10 min of incubation with [3H]thymidine with the virtual complete cessation of thymidine incorporation into the acid precipitate without any change in the thymidine triphosphate level. This late effect is not observed with podophyllotoxin and indicates a direct effect of VP-16-213 on DNA synthesis that is distinct from the earlier inhibitory effect on thymidine phosphorylation, which is secondary to membrane transport.

Versatile Services that Make Studying Easy
We write effective, thought-provoking essays from scratch
We create erudite academic research papers
We champion seasoned experts for dissertations
We make it our business to construct successful business papers
What if the quality isn’t so great?
Our writers are sourced from experts, and complete an obstacle course of testing to join our brigade. Ours is a top service in the English-speaking world.
How do I know the professor won’t find out?
Everything is confidential. So you know your student paper is wholly yours, we use CopyScape and WriteCheck to guarantee originality (never TurnItIn, which professors patrol).
What if it doesn’t meet my expectations?
Unchanged instructions afford you 10 days to request edits after our agreed due date. With 94% satisfaction, we work until your hair is comfortably cool.
Clients enjoy the breezy experience of working with us
Click to learn our proven method

from 11β and 4'-O-chloroacetyl-epi-podophyllotoxin ..


Etoposide, sold under the brand ..

The genus (Berberidaceae) has two species that are the most commercially exploited sources of podophyllotoxin; Wall. (syn. Royle) in India and Nepal and L. in the United States. Extracts of dried rhizome of Bankakri and mayapple were used by Himalayans and the North American native populations as cathartics and cholagogues respectively. In 1947, Hartwell and Shear demonstrated that a single dose of resin was effective in reducing tumors, but severe abdominal pains were associated with the treatment. Extracts containing natural lignan glycosides from were tested to eliminate side effects and provide better pharmacological results. The glycosides not only showed lower toxicity but also lower anticancer activity. These results led to the derivatization of podophyllotoxin, which lead to the development of etoposide and teniposide (Fig. 1).

this causes errors in DNA synthesis and promotes apoptosis of the ..

AB - A series of novel spin-labeled 4β-[(4-substituted)-1,2,3-triazol-1-yl]podophyllotoxin derivatives (17a-h) were firstly designed and synthesized with significant regioselectivity by employing Cu(I) catalyzed click approach, and evaluated for cytotoxicity against four human tumor cell lines (A-549, DU145, KB, and KBvin). Among them, compound 17h displayed the highest cytotoxic activity against the tumor cell lines tested. Significantly, compound 17h showed superior cytotoxic activity compared with etoposide (IC50 6.30 to >10 μM), a clinically available anticancer drug. Significant activity toward the drug resistant KBvin cell line revealed promising future for compound 17h as a new generation of epipodophyllotoxin-derived antitumor clinical trial candidate.

Total synthesis of (±) podophyllotoxin - ScienceDirect

N2 - A series of novel spin-labeled 4β-[(4-substituted)-1,2,3-triazol-1-yl]podophyllotoxin derivatives (17a-h) were firstly designed and synthesized with significant regioselectivity by employing Cu(I) catalyzed click approach, and evaluated for cytotoxicity against four human tumor cell lines (A-549, DU145, KB, and KBvin). Among them, compound 17h displayed the highest cytotoxic activity against the tumor cell lines tested. Significantly, compound 17h showed superior cytotoxic activity compared with etoposide (IC50 6.30 to >10 μM), a clinically available anticancer drug. Significant activity toward the drug resistant KBvin cell line revealed promising future for compound 17h as a new generation of epipodophyllotoxin-derived antitumor clinical trial candidate.

Total synthesis of (±) podophyllotoxin

This communication report the synthesis of 4--cyano-4-deoxy-4’-demethylepipodophyllotoxin, which is a important intermediate forsynthesizing 4- -carbon subtituted derivative. Chart 1.The synthetic approach started from podophyllotoxin(1).

Etoposide: a semisynthetic epipodophyllotoxin

The successful derivatization of podophyllotoxin into these potent antineoplastic drugs, etoposide and teniposide, has generated interest in structure optimization to produce new derivatives with superior pharmacological profiles and broader therapeutic uses. Numerous derivatives varying the etoposide basic structure have been proposed, synthesized, and clinically tested. Etopophos is a new etoposide phosphate designed to overcome the limitations associated with the poor solubility of etoposide. Etopophos can be administered intravenously at higher doses and rapidly converted by phosphatase in the plasma to etoposide, thus constituting an improvement in the treatment (Schacter 1996). NK 611, TOP 53, and GL 311 are among the most promising derivatives that attempt to increase the biological activities becoming more potent drugs than etoposide. These derivatives are in the first phase of clinical trials or pre-clinical developments (Huang et al. 1996; Pagani et al. 1996; Utsugi et al. 1996; Imbert 1998; Raßmann et al. 1999).

89%
of clients claim significantly improved grades thanks to our work.
98%
of students agree they have more time for other things thanks to us.
Clients Speak
“I didn’t expect I’d be thanking you for actually improving my own writing, but I am. You’re like a second professor!”