Academia.eduAcademia.edu

Outline

Title
Abstract
Introduction
References
All Topics
Chemistry
Chemicals and Drugs

Current development of podophyllotoxins

Profile image of Renzo CanettaRenzo Canetta

1982, Cancer Chemotherapy and Pharmacology

https://doi.org/10.1007/BF00254528
visibility

…

description

6 pages

link

1 file

Abstract

The unique biological properties and therapeutic efficacy of the podophyllotoxin derivatives, Vumon (VM26, teniposide) and Vepesid etoposide), are stimulating the interest of both laboratory and clinical researchers. Investigations on new pharmaceutical formulations, pharmacokinetics and metabolism are providing more appropriate information on drug administration; experimental chemotherapy indicates that, among others, cytosine arabinoside and cisplatin are highly synergistic with podophyllotoxins; single agent and combination treatment clinical trials are defining the respective role of Vumon and Vepesid in cancer chemotherapy.

Related papers

Podophyllotoxin derivative VP 16-213
a vp

Cancer Chemotherapy and Pharmacology, 1979

VP 16-213, a derivative of podophyllotoxin, is currently entering phase-III studies. Its mode of action is incompletely understood, but differs markedly from that of its parent compound. The greatest lethal damage is experienced by cells in the late S and G2 phases. In the L1210 system the drug shows marked schedule dependency: prolonged administration may be more effective than single bolus administration. As a single agent, VP 16-213 is the most active compound yet tested against small-cell bronchial carcinoma. It may also prove to be a useful agent in patients with other types of lung tumour, testicular teratomas, and some types of leukaemia. No long-term or cumulative toxicity has been reported. Most side effects are predictable and reproducible.

View PDFchevron_right
Adva-27 a , a Novel Podophyllotoxin Derivative Found to Be Effective against Multidrug Resistant Human Cancer Cells
Myriam Jean

2012

Background/Aim: Multidrug resistance poses a serious challenge in cancer therapy. To address this problem, we designed and synthesized Adva-27a, a novel non-ester GEM-difluorinated C-glycoside derivative of podophyllotoxin. Materials and Methods: Adva-27a activity was evaluated in a variety of assays including inhibition of topoisomerase IIα, cytotoxic activity in drug-sensitive and drug-resistant cancer cell lines, metabolic stability in human liver microsomes and pharmacokinetic properties in rats. Results: Adva-27a exhibited dose-dependent human topoisomerase IIα inhibitory activity and dose-dependent growth inhibitory activity in several drugsensitive and two multidrug-resistant cancer cell lines. In the multidrug-resistant cell lines, MCF-7/MDR (breast cancer) and H69AR (small-cell lung cancer), Adva-27a was significantly more potent than etoposide. The metabolic stability of Adva27a in human liver microsomes and its pharmacokinetic properties in rats were better than those of ...

View PDFchevron_right
Synthesis of 4β-amido and 4β-sulphonamido analogues of podophyllotoxin as potential antitumour agents
Sunanda Dastidar

Bioorganic & Medicinal Chemistry, 2003

The new 4b-amido analogues of podophyllotoxin or 4 0 -O-demethylepipodophyllotoxin have been prepared either by the coupling of 4b-amino podophyllotoxin or 4b-amino-4 0 -O-demethyl epipodophyllotoxin with the corresponding acids in presence of DCC in dichloromethane or by treating the appropriate acid chloride or sulphonyl chloride in presence of Et 3 N. These 4b-amido and 4b-sulphonamido derivatives of podophyllotoxin have been evaluated for their cytotoxicity against six human cancer cell lines. Some of these analogues have shown promising anticancer activity. #

View PDFchevron_right
Synthesis of 4-amido and 4-sulphonamido Analogues of Podophyllotoxin as Potential Antitumour Agents
Arifudidn Mohammed

—The new 4b-amido analogues of podophyllotoxin or 4 0-O-demethylepipodophyllotoxin have been prepared either by the coupling of 4b-amino podophyllotoxin or 4b-amino-4 0-O-demethyl epipodophyllotoxin with the corresponding acids in presence of DCC in dichloromethane or by treating the appropriate acid chloride or sulphonyl chloride in presence of Et 3 N. These 4b-amido and 4b-sulphonamido derivatives of podophyllotoxin have been evaluated for their cytotoxicity against six human cancer cell lines. Some of these analogues have shown promising anticancer activity.

View PDFchevron_right
Synthesis and anticancer activity of heteroaromatic linked 4β-amido podophyllotoxins as apoptotic inducing agents
lakshma nayak

Bioorganic & Medicinal Chemistry Letters, 2013

View PDFchevron_right
Anticancer activity and possible mode of action of 4-O-podophyllotoxinyl 12-hydroxyl-octadec-Z-9-enoate
Guoyi Ma

Lipids, 2005

4-O-Podophyllotoxinyl 12-hydroxyl-octadec-Z-9enoate (PHEFE) is a structurally novel FA analog of podophyllotoxin. In the present study, in vitro effects of PHEFE on a panel of 60 human tumor cell lines and its potential modes of anticancer action were investigated. PHEFE exhibited strong growth-inhibitory action in a number of solid tumor cells in vitro. It did not inhibit tubulin polymerization as podophyllotoxin does; rather, it inhibited the catalytic activity of topoisomerase II. Flow cytometry and staining assay with 4,6-diamidine-2-phenylindole dihydrochloride showed that PHEFE blocked the cell cycle at the G 2 /M phase and induced apoptosis in HL-60 cells. These analyses suggest that PHEFE has promising anticancer characteristics that differ from podophyllotoxin and etoposide.

View PDFchevron_right
Synthesis and Cytotoxicity of Novel Analogues of Podophyllotoxin
IOSR JPBS

We have synthesized four novel derivatives of podophyllotoxin, the chalcone derivatives namely 2-benzylidene-6,7-dimethoxy-4-phenyl-3,4-dihydro-2H-naphthalen-1-one (4a), 2-benzylidene-5,7-dichloro-6-hydroxy-4-phenyl-3,4-dihydro-2H-naphthalen-1-one(4b), and the amino-thiazolyl derivatives namely7,8-dimethoxy-5-phenyl-4,5-dihydro-naphtha[1,2-d] thiazol-2-yl amine (5a) and 2-amino-6,8-dichloro-5-phenyl-4,5-dihydro-naphtho[1,2-d] thiazol-7-ol (5b). The aryl tetralin ring system in these compounds were attached to a fused aminothiazolyl ring or a chalcone ring. Synthesis of the tetralin ring in these podophyllotoxin derivatives was accomplished by the cyclization of the γ-hydroxyketones. These derivatives were evaluated for the induction of cytotoxicity in mouse mammary carcinoma cells in vitro. All the four compounds exhibited time dependent cytotoxicity at a concentration of 100µM when assessed by Trypan blue dye exclusion assay on Ehrlich Ascites Tumor (EAT) cells in vitro.

View PDFchevron_right
Synthesis of 4beta-amido and 4beta-sulphonamido analogues of podophyllotoxin as potential antitumour agents
Sunanda Dastidar

Bioorganic & Medicinal Chemistry

The new 4beta-amido analogues of podophyllotoxin or 4'-O-demethylepipodophyllotoxin have been prepared either by the coupling of 4beta-amino podophyllotoxin or 4beta-amino-4'-O-demethyl epipodophyllotoxin with the corresponding acids in presence of DCC in dichloromethane or by treating the appropriate acid chloride or sulphonyl chloride in presence of Et(3)N. These 4beta-amido and 4beta-sulphonamido derivatives of podophyllotoxin have been evaluated for their cytotoxicity against six human cancer cell lines. Some of these analogues have shown promising anticancer activity.

View PDFchevron_right
Preparation and cytotoxicity of podophyllotoxin derivatives lacking the lactone ring
Arturo San Feliciano

Tetrahedron, 1997

Several eyclolignans lacking of the lactone moiety can easily be prepared from naturally occurring lignans such as podophyllotoxin and deoxypodophyllotoxin by simple chemical transformations. Their cytotoxicity has been studied in four tumoral cell lines. Most of the compounds show similar effects in all the neoplastic systems tested, except the aldehyde 9 (methyl 9-deoxy-9-oxo-ct-apopicropodophyllate) and the hydrazones 16 and 17 which show a highly selective cytotoxicity towards HT-29 human colon carcinoma. Additionally, several molecular modeling studies have been done with aldehyde 9 and the corresponding saturated aldehyde 13 in comparison with podophyllotoxin. © 1997 Elsevier Science Ltd.

View PDFchevron_right
Investigation of podophyllotoxin esters as potential anticancer agents: Synthesis, biological studies and tubulin inhibition properties
Neha Dhoke

European Journal of Medicinal Chemistry, 2015

A series of fifteen podophyllotoxin derived esters have been synthesized and their anti-cancer properties have been evaluated against A549 (lung cancer), DU-145 (prostate cancer), HepG2 (liver cancer), HeLa (cervical cancer) and MCF-7 (breast cancer) cell lines. Five compounds of the series 8a, 8geh, 8m and 8o showed IC 50 values in the range of 0.71e10.94 mM. Among compounds, 8g and 8h showed significant cytotoxicity towards all the types of cancer studied. Cell cycle analysis revealed that the compounds 8a, 8m and 8o inhibit proliferation by cell cycle arrest. Also Hoechst-positive nucleus indicating apoptosis of these cells was observed in presence of 8geh. Further studies revealed that these compounds inhibit tubulin polymerization and leads to the inactivation of AKT/PKB that are known to play an important role in the proliferation of cancer cells.

View PDFchevron_right

References (63)

  1. Abeloff MD, Ettinger DS, Khouri NF, Lenhard RE (1979) Intensive induction therapy for small cell carcinoma of the lung. Cancer Treat Rep 63:519
  2. Aisner J, Whitacre M, VanEcho DA, Esteroy R J, Wiernik PH (1980) Alternating non-cross resistant combination chemo- therapy for small cell carcinoma of the lung (SCCL). Proc Am Soc Clin Oncol 21:453
  3. Anonymous (1981) Vepesid (Etoposide) Current clinical experience. Bristol-Myers, New York, p 4
  4. Arnold AM (1979) Podophyllotoxin derivative VP16-213. Cancer Chemother Pharmacol 3:71
  5. Arnold AM, Dodson M, Renwick A, Whitehouse JMA (1980) Pharmacokinetics of VP16-213 using a new HPLC assay. Cancer Chemother Pharmacol [Suppl] 5:2
  6. Beveridge T, Kalberer F, Nuesch E (1974) Bioavallability study with 3H-VP16-213. Internal report. Sandoz, Basel
  7. Bleyer WA, Chard RL Jr, Krivit W, Hammond D (1978) Epipodophyllotoxin therapy of childhood neoplasia: a com- parative phase 2 analysis of VM26 and VP16-213. Proc Am Soc Clin Oncol 19:373
  8. Bleyer WA, Krivit W, Chard RL Jr, Hammond D (1979) Phase II study of VM26 in acute leukemia, neuroblastoma, and other refractory childhood malignancies: a report from the Children's Cancer Study Group. Cancer Treat Rep 63:977
  9. Broder LE, Selawry OS, Johnson MK (1979) Treatment of small cell carcinoma (SCC) of the lung utilizing mutually non-cross-resistant chemotherapy regimens. Proc Am Ass Cancer Res 20:278
  10. Brunner KW, Sonntag RW, Ryssel HJ, Cavalli F (1976) Comparison of the biologic activity of VP16-213 given iv and orally in capsules or drink ampules. Cancer Treat Rep 60: 1377
  11. Burchenal JH, Kalaher K, Dew K, Lokys L, Gale G (1978) Studies of cross-resistance, synergistic combinations and blocking of activity of platinum derivatives. Biochemie 60: 961
  12. Cabanillas F, Gutterman JV, Bodey GP, Freireich EJ (1980) Improvement in complete remission (CR) rate and dis- ease-free survival (DFS) of lymphomas by sequential use of non-cross-resistant induction regimens, late intensification (LI) and immunotheraphy (IT). Proc Am 8oc Clin Oncol 21 : 466
  13. Cabanillas F, Hagemesister F, Bodey GP, Freireich EJ (1981) Ifosfamide, Methotrexate, VP16, (IMVP16), an effective salvage regimen for lymphoma. Proc Am Soc Clin Oncol 22:517
  14. Cavalli F, Hasler E, Ryssel HJ, Sonntag RW, Brunner KW (1977) A combination of cyclophosphamide, methotrexate, vincristine and VP16-213 (NSC 141540) in the treatment of bronchogenic carcinoma. Tumori 63:169
  15. Cavalli F, Sonntag RW, Jungi F, Senn HJ, Brunner KW (1978) VP16-213 monotherapy for remission induction of small cell lung cancer: a randomized trial using three dosage schedules. Cancer Treat Rep 62:473
  16. Chard RL Jr, Krivit W, Bleyer WA, Hammond D (1979) Phase II study of VP16-213 in childhood malignant disease: a Children's Cancer Study Group. Cancer Treat Rep 63 : 1755
  17. Chiuten DF, Wodinsky I, Abraham D (1979) Influence of treatment schedule on the toxicity and antitumor activity of mitotic inhibitors and semi-synthetic podophyllotoxin deriva- tives. Proc Am Soc Clin Oncol 20:402
  18. Creaven PJ, Allen LM (1975) EPEG, a new antineoplastic epipodophyllotoxin. Clin Pharmacol Ther 18:221
  19. Creaven P J, Alien LM (1975) PTG, a new antineoplastic podophyllotoxin. Clin Pharmacol Ther 18:227
  20. Creaven PJ, Newman SJ, Selawry OS, Cohen MH, Primack A (1974) Phase I clinical trial of 4-Demethylpodophyllotoxin 9-4 (4,6-0-Ethylidene-B-D-glucopyranoside) (NSC-141540; VP16-213). Cancer Chemother Rep 58:901
  21. D'Incalci M, Farina P, Fasoli M, Marsoni S (1981) VP16 Plasma levels after iv and two methods of oral administration to choriocarcinoma patients. Proc Am Soc Clin Oncol 22: 357
  22. Dombernowsky P, Nissen NI (1976) Combination chemother- apy with 4-Demethylepipodophyllotoxin 9-(4,6-0-ethyli- dene-B-D-glucopyronoside), VP16-213 (NSC 141540) in L1210 Leukemia. Eur J Cancer 12:181
  23. Drewinko B, Green C, LiLoo T (1976) Combination chemo- therapy in vitro with cisdichlorodiammineplatinum (II). Can- cer Treat Rep 60:1619
  24. Eagan RT, Lee RE, Frytak S, Ingle JN, Creagan ET (1980) Combination chemotherapy (CCT) with and without cis-diam- minedichloroplatinum (II) plus thoracic radiation therapy (TRT) for limited small cell lung cancer (SCLC). Proc Am Ass Cancer Res 21:131
  25. Eckhardt S, Dobrentey E, Bodrogi I (1975) Results obtained with combination therapy of VM26, Natulan and Prednisolone in generalized Hodgkin's Disease. Chemotherapy 21:248
  26. Evans WE, Sinkule JA, Horvath A, Crom WR, Dow LW, Rivera G (1981) Clinical pharmacology of VM26 (NSC 122819) and VP16 (NSC 141540) in children with cancer. Proc Am Ass Cancer Res 22:174
  27. Fisher RI, DeVita VT, Hubbard SM, Brennan MF, Chabner BA, Simon R, Young R (1980) ProMACE-MOPP combina- .on chemotherapy: treatment of diffuse lymphomas. Proc Am Soc Clin Oncol 21:468
  28. Goldhirsch A, Joss RA, Cavalli F, Sonntag RW, Brunner KW (1981) Cis-dichloradiammineplatinum (II) and VP16-213 com- bination chemotherapy for non-small cell lung cancer. Med Pediatr Oncol 9:205
  29. Holoye IY, Samuels ML, Lanzotti VJ, Smith T, Barkley HT JR (1977) Combination chemotherapy and radiation therapy for small cell carcinoma of the lung. JAMA 2:1221
  30. Issell BF, Crooke ST (1979) Etoposide (VP16-213). Cancer Treat Rev 6:107
  31. Issell BF, Tihon C, Curry ME (1981) Etoposide (VP16) and Teniposide (VM26) comparative in vitro activities in human tumors. Proc Am Ass Cancer Res 22:233
  32. Lau ME, Hansen HH, Pedersen H (1979) Phase I trial of a new form of an oral administration of VP16-213. Cancer Treat Rep 63: 485
  33. Lelieveld P, Smink T, Van Putten L (1978) Experimental studies on the combination of radiation and chemotherapy. Int J Radiat Oncol Biol Phys 4:37
  34. Longeval E, DeJager R, Tagnon H, Klastersky J (1980) Cisplatin (CDDP)-VP16-213 combination chemotherapy in non small cell (NSC) bronchogenic carcinoma: phase I-II clinical trial. Proc Am Soc Clin Oncol 21:368.
  35. Mabel JA (1979) Therapeutic synergism in murine tumors for combinations of cis-diamminedichloroplatinum with VP16-213 or BCNU. Proc Am Ass Cancer Res 20:230
  36. Minna JD, Ihde D, Burn PA, Cohen M, Fossiek B, Mathews MJ (1980) Extensive stage small cell carcinoma of the lung (SCCL): effect of increasing intensity of induction chemo- therapy. Proc Am Soc Clin Oncol 21:448
  37. Natale R, Hilaris B, Wittes R (1980) Prolonged remission of small cell lung carcinoma (SCCL) with intensive chemother- apy induction and high radiation therapy without mainte- nance. Proc Am Soc Clin Oncol 21:452
  38. Nissen NI, Larsen V, Pedersen H, Thomsen K (1972) Phase I clinical trial of a new antitumor agent, 4-demethyl-epipodo- phyllotoxin 9-(4,6-0-ethylidene-B-D-glucopyranoside (NSC 141540; VP16-213). Cancer Chemother Rep 56:769
  39. Nissen NI, Hansen HH, Pedersen H, Stryer I, Dombernowsky P, Hessellund M (1975) Clinical trial of the oral form of a new podophyllotoxin derivative, VP16-213 (NSC-141540), in patients with advanced neoplastic disease. Cancer Chemother Rep 59 : 1027
  40. Nissen NI, Dombernowsky P, Hansen HH, Larsen V (1976) Phase I clinical trial of an oral solution of VP16-213. Cancer Treat Rep 60:943
  41. Nissen NI, Dombernowsky P, Hansen HH, Pedersen AG (1980) The epipodophyllotoxin derivatives VM26 and VP16-213, 1976-1979, a review. Recent Results Cancer Res 74:98
  42. Osoba D, Evans WK, Feld R (1981) VP16 and cis-platinum (P) combination chemotherapy for relapse in small cell lung. Proc Am Soc Clin Oncol 22:495
  43. Pendergrass KB, Abeloff MD, Ettinger DS, Burke PT, Order SE, Khouri N (1980) Intensive timed sequential combination chemotherapy and adjunctive radiotherapy in extensive stage small cell carcinoma of the lung (SCC). Proc Am Soc Clin Oncol 21 : 447
  44. Pinedo HM (1980) In: First International Congress for Advances in Cancer Chemotherapy, Cairo
  45. Radice PA, Bunn PA Jr, Ihde DC (1979) Therapeutic trials with VP16-213 and VM26: active agents in small cell lung cancer, non-Hodgkin's lymphomas, and other malignancies. Cancer Treat Rep 63:1231
  46. Rivera G, Avery T, Roberts D (1975) Response of L1210 to combinations of cytosine arabinoside and VM26 or VP16-213. Eur J Cancer 11:639
  47. Rivera G, Avery T, Pratt C (1975) 4'-Demethylepipodo- phyllotoxin
  48. NSC-122819; VM26) and 4'-Demethylepipodophyllotoxin
  49. VP16-213) in childhood cancer: preliminary observations. Cancer Treat Rep 59:743
  50. Rivera G, Dahl GV, Bowman WP, Avery TL, Wood A, Aur RJ (1980) VM26 and cytosine arabinoside combination chemotherapy for initial induction failures in childhood lymphocytic leukemia. Cancer 46:1727
  51. Samson MK, Baker LH, Talley RW, Fraile 1LI (1978) VM26 (NSC-122819): a clinical study in advanced cancer of the lung and ovary. Eur J Cancer 15:1395
  52. Santoro A, Bonfante V, Bonadonna G (1981) Phase II study of etoposide (VP16) in malignant lymphomas and solid tumors. In: New drugs for cancer therapy in the Eighties. Rome, p 81
  53. Schabel FM Jr, Trader MW, Laster WR Jr, Corbett TH, Griswold DP Jr (1979) Cis-dichlorodiammineplatinum (II): combination chemotherapy and cross-resistance studies with tumors of mice. Cancer Treat Rep 63:1459
  54. Seeber S, Osieka R (1981) Comparative biochemical analyses in Ehrlich ascites (EAT) resistant to Daunorubicin (DNR), Etoposide (VP16) and cisplatin (DDP). Patterns of cross-re- sistance and collateral sensitivity. Proc Am Ass Cancer Res 22:257
  55. Sierocki JS, Hilaris BS, Hopfan S, Martini N, Barton D, Golbey RB, Wittes RE (1979) Cis-dichlorodiammineplatinum (II) and VP16-213: an active induction regimen for small cell carcinoma of the lung. Cancer Treat Rep 63:1593
  56. Snodgrass W, Walker L, Heideman R, Odom LF, Hays T, Tubergen DG (1980) Kinetics of VP16 epipodophyllotoxin in children with cancer. Proc Am Soc Clin Oncol 21:333
  57. Soloway MS, Masters SB, Murphy WM (1980) Cisplatin analogs and combination chemotherapy in the therapy of murine bladder cancer. In: Cisplatin, current status and new developments. Academic Press, New York, p 345 55. Stahelin H (1970) 4-Demethyl-epipodophyllotoxin thenyli- dene glucoside (VM 26), a podophyllum compound with a new mechanism of action. Eur J Cancer 6:303
  58. Stahelin H (1973) Activity of a new glycosidic lignan derivative (VP16-213) related to podophyllotoxin in experimental tumors. Eur J Cancer 9:215
  59. Strife RJ, Jardine I, Colvin M (1980) Analysis of the anticancer drugs VP16-213 and VM26 and their metabolites by high-per- formance liquid chromatography. J Chromatogr 182:211
  60. Valdivieso M, Cabanillas F, Bedikian AY, Mountain CF, Barkley HT, Bodey GP (1979) Intensive induction chemo- therapy (IIC) of small cell lung cancer (SCLC) with ECHO: EpipodophyUotoxin VP16, C = Cytoxan, H = Hydroxydau- norubicin, O = Oncovin. Proc Am Soc Clin Oncol 20:383
  61. Williams SD, Einhorn LH, Greco FA, Oldham R, Fletcher R (1980) VP16-213 salvage therapy for refractory germinal neoplasms. Cancer 46:2154
  62. Woods RL, Fox RM, TattersaU MHN (1979) Treatment of small cell bronchogenic carcinoma with VM26. Cancer Treat Rep 63 : 2011
  63. Accepted July, 1981

Related papers

Podophyllotoxin: Current Perspectives
MOHD ADIL

Podophyllotoxin is a naturally occurring lignan with important antineoplastic and antiviral properties and supported by detailed understanding of their mechanism of action, and facilitated by chemical manipulations that have amplified their bioactivity, the podophyllotoxin analogues have advanced to the forefront of several areas of therapeutic and developmental chemotherapy. Additive and synergistic laboratory interactions with other cytotoxic drugs have been exploited to allow development of podophyllotoxin-based multidrug regimens, which are showing important activity in several malignancies, and many of its related analogues will complement conventional pharmaceuticals in treatment, prevention and diaganosis of disease, while at the same time adding value to agriculture. Additive and synergistic laboratory interactions with other cytotoxic drugs have been exploited to allow development of etoposide-based multidrug regimens, which are showing important activity in several malignancies. Extensive structural modifications of podophyllotoxin have been performed in order to obtain more potent and less toxic antitumour agents, which resulted in the widespread clinical introduction of two semisynthetic glucoconjugate analogues of etoposide and teniposide and newer agents with promising preclinical activity are in various stages of clinical assessment. As knowledge of molecular and biochemical mechanisms of action and resistance continues to expand, newer and better podophyllotoxin-based strategies for treatment of malignant disease are likely to evolve. This review provides a detailed discussion of research advances in the synthetic and medicinal chemistry of podophyllotoxin, and addresses the short history and pharmacological action of these compounds and further outlines the preclinical development and clinical trials of drugs in the pipeline and marketing approval. Finally, a systemic evaluation of novel and important analogues of podophyllotoxin and their contribution to the current structure-activity profile are considered. It is hoped that this review will be able to address the contributions of podophyllotoxin-related research to overall drug discovery and development and the role that this field will play in future.

View PDFchevron_right
Investigation of podophyllotoxin esters as potential Anti-cancer agents
MOHD ADIL

A series of fifteen podophyllotoxin derived esters have been synthesized and their anti-cancer properties have been evaluated against A549 (lung cancer), DU-145 (prostate cancer), HepG2 (liver cancer), HeLa (cervical cancer) and MCF-7 (breast cancer) cell lines. Five compounds of the series 8a, 8geh, 8m and 8o

View PDFchevron_right
VP16-213 and podophyllotoxin
John Loike

Cancer Chemotherapy and Pharmacology, 1982

VP16-213, a semi-synthetic derivative of podophyllotoxin, is an effective antitumor agent in the treatment of a variety of leukemias and solid tumors. A comparison of the mechanism of action of VP16-213 and podophyllotoxin has revealed that although both drugs inhibit the uptake of nucleosides into HeLa cells, they exhibit other biological properties which are quite distinct. Podophyllotoxin is a potent inhibitor of microtubule assembly in vitro, while VP16-213 has no effect in this system. VP16-213 induces single stranded breaks in HeLa cell DNA, an effect which may be related to its antitumor activity. In contrast to VP16-213-treated cells, podophyllotoxin-treated cells maintain DNA integrity. Structure-activity relationship studies have identified some of the chemical sites of VP16-213 and podophyllotoxin responsible for each of their biological properties. These studies illustrate that chemical modification of podophyllotoxin can generate derivatives which possess new and unique biological properties.

View PDFchevron_right
4-Aza-Podophyllotoxins: synthesis and use as anti-cancer agents
Khaya Timothy Gould

2020

Thesis (MSc)--Stellenbosch University, 2020.ENGLISH ABSTRACT: Podophyllotoxins, and their derivatives, have shown significant anti-proliferative properties. Etoposide and other semi-synthetic analogues, such as teniposide, have been successfully employed as clinical anti-cancer agents. 4-Aza-podophyllotoxins, which are structurally simplified synthetic analogues of podophyllotoxin, have been successfully synthesised and have shown comparable biological activity to the naturally occurring (-) podophyllotoxin. To further investigate the method of inhibition of this class of compounds, which have been reported to act as either tubulin inhibitors or topoisomerase II poisons, two libraries of 4-aza-podophyllotoxin analogues were synthesised. The biological test results from the first library of analogues was used to inform the synthesis of a second library of compounds. The first library contains a diverse group of twelve 4-aza- podophylltoxin analogues, six with differences in the 4N- p...

View PDFchevron_right
Podophyllotoxin: History, Recent Advances and Future Prospects
aamir mushtaq

2021

Podophyllotoxin, along with its various derivatives and congeners are widely recognized as broad-spectrum pharmacologically active compounds. Etoposide, for instance, is the frontline chemotherapeutic drug used against various cancers due to its superior anticancer activity. It has recently been redeveloped for the purpose of treating cytokine storm in COVID-19 patients. Podophyllotoxin and its naturally occurring congeners have low bioavailability and almost all these initially discovered compounds cause systemic toxicity and development of drug resistance. Moreover, the production of synthetic derivatives that could suffice for the clinical limitations of these naturally occurring compounds is not economically feasible. These challenges demanded continuous devotions towards improving the druggability of these drugs and continue to seek structure-optimization strategies. The discovery of renewable sources including microbial origin for podophyllotoxin is another possible approach. ...

View PDFchevron_right

Related topics

  • Pharmaceutical Chemistry
  • Combination drug therapy
  • Drug Compounding
  • Pharmaceutical Formulation

    • Cited by

    Design and Synthesis of 4-O-Podophyllotoxin Sulfamate Derivatives as Potential Cytotoxic Agents
    Ashraf N A B I E L Abdalla

    Evidence-Based Complementary and Alternative Medicine

    4-O-Podophyllotoxin sulfamate derivatives were prepared using the natural lignan podophyllotoxin. The prepared compounds were afforded by reacting O-sulfonyl chloride podophyllotoxin with ammonia or aminoaryl/heteroaryl motif. Biological evaluation was performed in human breast cancer (MCF7), ovarian cancer (A2780), colon adenocarcinoma (HT29), and normal lung fibroblast (MRC5) cell lines. Compound 3 exhibited potent inhibitory activity and good selectivity margin. Compounds 2, 3, and 7 exerted apoptotic effect in MCF7 cells in a dose-dependent manner. The cytotoxicity of the verified compounds was inferior to that of podophyllotoxin.

    View PDFchevron_right
    580 California St., Suite 400
    San Francisco, CA, 94104
    © 2025 Academia. All rights reserved