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At least 217 records · Page 12Linked to original sources
PubMedDate not supplied

Penile condylomata acuminata: an experimental model for evaluation of topical self-treatment with 0.5--1.0% ethanolic preparations of podophyllotoxin for three days.

Penile condylomata were eradicated from 22 (54%) of 41 men whose lesions were painted twice (with a 72-hr interval) by the investigator with 8% podophyllotoxin in ethanol and from 83 (48%) of 173 men who self-administered either 0.5 to 1.0% topical preparations twice or thrice daily for three subsequent days. All regimens had identical efficacy; a higher frequency of mild local irritation in the self-medicating group may be outweighed by a relatively lower risk for hazardous systemic absorption. The rate of cure was higher when tumors afflicted the preputial cavity than the urinary meatus or penile skin and was lower when there were more than five warts, lesions grew in a plaque-like pattern, or duration of warts exceeded six months. Sixty-six men were sensitized with 2,4-dinitrochlorobenzene; the degree of response to subsequent challenge did not correlate to number or growth pattern of lesions or to cure rate.

Administration, Topical↗
PubMed1993

[In vitro comparison of podophyllotoxin analogues; etoposide, teniposide and NK 611 using human lung cancer cell lines].

In an attempt to predict the antitumor activity of a new podophyllotoxin analogue, NK 611, in the treatment of lung cancer, we compared the drug with etoposide and teniposide using four human small cell lung cancer (SCLC) cell lines, SBC-2, -3, -4, -7, and two non-small cell lung cancer cell lines, ABC-1, EBC-1. In terms of the fifty percent tumor growth inhibitory concentration (IC 50) determined by MTT assay, teniposide was most potent among the drugs. The degree of cross-resistance of each drug was investigated using an etoposide-resistant SCLC subline (SBC-3/ETP), an adriamycin-resistant subline (SBC-3/ADM 100), and a cisplatin-resistant subline (SBC-3/CDDP). As for relative resistant (the ratio of IC 50 for resistant subline to that for the parent subline), NK 611 was least cross-resistant to etoposide, adriamycin, and cisplatin among drugs tested. These results indicate that NK 611 may play a role in a salvage chemotherapy for patients with resistant SCLC.

Adenocarcinoma↗
PubMed1993

Synthesis and biological activity of novel thymidine derivatives of podophyllotoxin and 4'-demethylepipodophyllotoxin.

We have synthesized a number of novel derivatives of podophyllotoxin (POD) and 4'-demethylepipodophyllotoxin (DMEP) in which the nucleoside thymidine has been conjugated at the C4 position. To investigate the structure-activity relationship among these compounds, the cross-resistance patterns of these derivatives towards a set of either POD-resistant (PodR) or VP16/VM26-resistant (VpmR) mutants of Chinese hamster ovary (CHO) cells were determined. These mutants exhibit highly specific cross-resistance patterns toward compounds that show either POD- or VP16/VM26-like activity. The observed cross-resistance patterns of the thymidine derivatives suggests that these compounds display POD-like activity in vivo and show no VP16/VM26-like activity. Further, treatment of Chinese hamster cells with these compounds caused a dose-dependent increase in the mitotic index similar to the patterns observed with POD and DMEP, supporting the data from the cross-resistance assay. Most thymidine derivatives exhibited much lower activity in comparison to POD or DMEP, suggesting that the thymidine moiety interferes with the interaction of these compounds with the receptor site on the tubulin molecule. One of these derivatives which was most active in the aforementioned assays was also found to be a competitive inhibitor of radiolabelled POD binding to purified bovine brain tubulin. All other compounds were insoluble at concentrations required to perform the competition assay. Molecular modelling studies provide valuable insight regarding the three-dimensional structural requirements that distinguish POD-like compounds from their VP16/VM26-like counterparts. There appears to be a very limited spatial and electrostatic requirement for the bulky glycosidic moiety at C4 which is essential for VP16/VM26-like activity.

Animals↗
PubMedDate not supplied

[A multivariate analysis approach to antineoplastic and antiviral structure-activity relationships to a series of podophyllotoxins].

In this work, the authors have used technics of multivariate analysis to determine the structure-activity relationships of 46 podophyllotoxin derivatives and analogs studied for their antineoplastic and antiviral activities. The obtained results allow to envisage the possible synthesis of more specific molecules by making modifications in the structure of the model molecular archetype.

Animals↗
PubMed2004

Anti-AIDS agents. Part 61: Anti-HIV activity of new podophyllotoxin derivatives.

A series of novel podophyllotoxin derivatives containing structural modifications at C-4 (7-14), C-4' (16-17), and the methylenedioxy A-ring (23-28) was synthesized and tested for inhibition of HIV replication. Four of these compounds (25-28) were previously reported to show EC(50) values of <0.001 microg/mL and therapeutic index (TI) values >120. Three of the newly tested compounds (8, 12, and 20) showed good activity with EC(50) values of 0.012, <0.001, and 0.389 microg/mL and TI values of 19.1, >16, and 19.4, respectively. A comparison of the anti-HIV activity of these derivatives suggested that an opened A-ring with 6,7-dimethoxy substitution and a 4'-demethylated E ring enhanced anti-HIV activity.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Determination of a new podophyllotoxin derivative, TOP-53, and its metabolite in rat plasma and urine by high-performance liquid chromatography with electrochemical detection.

A high-performance liquid chromatographic method was developed for the determination of a new podophyllotoxin derivative, TOP-53 (I), and TOP-53 glucuronide (II) as its major metabolite in rat plasma and urine. For the analysis of I, the sample was chromatographed on a reversed-phase C18 column with electrochemical detection after consecutive two-step liquid-liquid extractions. Compound II was determined as I after enzymatic hydrolysis of II. This method was validated sufficiently with respect to specificity, accuracy, and precision. The limits of quantitation for both I and II were 2 ng/ml in plasma and 10 ng/ml in urine. The method is thus useful for the pharmacokinetic study of I.

Animals↗
PubMed2003

Dearomatizing cyclization of arylsulfonylalkoxymethyl lithiums: a route to the podophyllotoxin skeleton.

[reaction: see text] The phenylsulfonyl group promotes the dearomatizing cyclization of tethered organolithiums onto aromatic rings. With an ether tether, the cyclizations create a new tetrahydrofuran ring, and both cyclization and subsequent electrophilic quenches proceed with high levels of diastereoselectivity. The sulfonyl group can be removed from the cyclized products oxidatively or reductively. The dearomatizing cyclization of a naphthyl sulfone was used in the synthesis of a close structural analogue of podophyllotoxin.

Journal Article↗
PubMed1992

Clinical pharmacology and schedule dependency of the podophyllotoxin derivatives.

Etoposide and teniposide are closely related derivatives of podophyllotoxin, and both have a phase-specific action in the late S and early G2 phases of the cell cycle. Etoposide has attracted more widespread use and study, although no evidence suggests a differing mode of action or spectrum of anticancer activity. The drugs have significant differences in their clinical pharmacology, however. Teniposide exhibits greater protein-binding affinity, has a longer plasma terminal elimination half-life, and has reduced plasma and renal clearances. Little is accurately known about the metabolism of either drug, but the fact that 40% to 60% of administered etoposide is accounted for by excretion or metabolism, whereas the range is only 10% to 25% for teniposide, reflects a further difference between the drugs. Renal dysfunction impairs etoposide excretion, but the effect of hepatic impairment on drug clearance is unclear. A specific oral formulation exists only for etoposide, although the unpalatable intravenous preparations of both drugs can be taken orally. The bioavailability of oral etoposide is about 50% at doses of 200 mg or less and decreases as drug doses increase. There is considerable intrapatient and interpatient variation in etoposide absorption, but the reasons for this are unknown. In vitro, the efficacy of etoposide is highly dependent on the schedule of administration. The superior efficacy without increased toxicity of more prolonged schedules of etoposide administration has been demonstrated recently in patients with small cell lung cancer (SCLC). Although the optimal schedule in any specific tumor is not known, current pharmacodynamic evidence suggests that the efficacy of etoposide, at least in SCLC, is related to the maintenance of prolonged low blood concentrations of drug.

Chemical Phenomena↗
PubMed1996

Antitumor activity of a novel podophyllotoxin derivative (TOP-53) against lung cancer and lung metastatic cancer.

We synthesized a potent new antitumor podophyllotoxin derivative (4beta-aminoalkyl-4'-O-demethyl-4-desoxypodophyllotoxin; TOP-53) in our search for a drug that has strong activity against lung cancer and lung metastatic cancer. TOP-53 exhibited twice the inhibitory activity of etoposide (VP-16) against topoisomerase II and induced DNA strand breaks but showed no inhibitory activity against tubulin polymerization. The in vitro cytotoxic activity of TOP-53 assessed as IC50 was 0.016-0.37 microg/ml and 0.26-8.9 microg/ml against marine tumor and human non-small cell lung cancer (NSCLC) cell lines, respectively. TOP-53 exerted significant efficacy equivalent to that of VP-16 on s.c.-implanted murine solid tumors (Colon 26, B16-BL6, and Lewis lung carcinoma) at doses 3-5 times lower than that of VP-16. In human tumor xenografts using NSCLC, TOP-53 was active for four of five tumors, whereas VP-16 was active for two of five tumors. Potent inhibitory activity of TOP-53 was also found against a lung tumor (Lewis lung carcinoma) and four lung metastatic tumors (NL-22 and NL-17 colon cancer, UV2237M fibrosarcoma, and K1735M2 melanoma). TOP-53 appeared to be more active against four of them than VP-16. Thus, TOP-53 is not only active against s.c.-implanted lung cancers but also strongly active against lung localized tumor and metastatic tumors in the lungs. The high selectivity of TOP-53 was attributed to its high distribution into the lung and its persistence. TOP-53 is expected to be highly effective against lung cancer including NSCLC and various lung metastatic tumors in the clinical field.

Animals↗
PubMed1988

Podophyllotoxins for brain metastases of small cell lung cancer.

A patient with brain metastases of small cell lung cancer (SCLC) responded initially to cranial irradiation. Recurrences were subsequently successfully treated with high-dose intravenous etoposide (VP 16-213) and teniposide (VM 26). Epipodophyllotoxins are potentially useful for CNS metastases of SCLC.

Brain Neoplasms↗