The primary in vitro antitumor screening of 'half-mustard type' phenothiazines

Mark A. Wuonola, Michael G. Palfreyman, Noboru Motohashi, Masami Kawase, Sabit Gabay, János Nacsa, J. Molnár

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The antitumor effects of 'half-mustard type' phenothiazines were studied on 57 different tumor cell lines, including leukemias, non-small lung cancer, colon, central nervous system, ovarian, renal, breast, and prostate cancer, as well as melanoma cell cultures. Alkyl-urea derivatives of phenothiazines displayed in vitro antitumor activity. The phenothiazine phthalimido derivatives (1-6) were not active on the majority of cancer cell cultures. In contrast, propyl-ureas (9, 11) were active against some leukemia cell types. Only two compounds with the butylene [(CH2)4] linker (10, 12) were active against non-small lung cancer cells. Compounds containing the propylene linker were less effective. On colon cancer lines, tumor cells from the central nervous system and on melanoma cells the same compounds were effective, however, having substituents at the 2-position of phenothiazine seems to be important. Surprisingly, the majority of ovarian cancer cell lines (except one type, IGROVI) and five of eight renal cancer lines were not sensitive to these phenothiazine derivatives. The two butylene linked phenothiazine ureas (10, 12) had moderate antiproliferative action on two renal cancer cell lines. The prostate cancer and some breast cancer cell lines were not sensitive. Nevertheless some breast cancer cell lines were apparently sensitive to CF3-substituted phenothiazine alkylureas. On the basis of these experiments one may postulate that in the case of insensitive cells an mdr-gene encoded multidrug resistance efflux pump is responsible for the resistance. The selectivity or organ cell specificity of the effective phenothiazines will be targeted for improvement in further studies, in order to avoid the general cytotoxic effects of 'half mustard type' phenothiazines.

Original languageEnglish
Pages (from-to)3409-3423
Number of pages15
JournalAnticancer Research
Volume17
Issue number5 A
Publication statusPublished - Sep 1997

Fingerprint

Phenothiazines
Mustard Plant
Kidney Neoplasms
Breast Neoplasms
Urea
Cell Line
Ovarian Neoplasms
Colonic Neoplasms
Melanoma
Prostatic Neoplasms
Leukemia
Cell Culture Techniques
MDR Genes
Central Nervous System Neoplasms
Organ Specificity
Tumor Cell Line
Non-Small Cell Lung Carcinoma
Lung Neoplasms
Central Nervous System
phenothiazine

Keywords

  • Antitumor activity
  • Phenothiazines

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Wuonola, M. A., Palfreyman, M. G., Motohashi, N., Kawase, M., Gabay, S., Nacsa, J., & Molnár, J. (1997). The primary in vitro antitumor screening of 'half-mustard type' phenothiazines. Anticancer Research, 17(5 A), 3409-3423.

The primary in vitro antitumor screening of 'half-mustard type' phenothiazines. / Wuonola, Mark A.; Palfreyman, Michael G.; Motohashi, Noboru; Kawase, Masami; Gabay, Sabit; Nacsa, János; Molnár, J.

In: Anticancer Research, Vol. 17, No. 5 A, 09.1997, p. 3409-3423.

Research output: Contribution to journalArticle

Wuonola, MA, Palfreyman, MG, Motohashi, N, Kawase, M, Gabay, S, Nacsa, J & Molnár, J 1997, 'The primary in vitro antitumor screening of 'half-mustard type' phenothiazines', Anticancer Research, vol. 17, no. 5 A, pp. 3409-3423.
Wuonola MA, Palfreyman MG, Motohashi N, Kawase M, Gabay S, Nacsa J et al. The primary in vitro antitumor screening of 'half-mustard type' phenothiazines. Anticancer Research. 1997 Sep;17(5 A):3409-3423.
Wuonola, Mark A. ; Palfreyman, Michael G. ; Motohashi, Noboru ; Kawase, Masami ; Gabay, Sabit ; Nacsa, János ; Molnár, J. / The primary in vitro antitumor screening of 'half-mustard type' phenothiazines. In: Anticancer Research. 1997 ; Vol. 17, No. 5 A. pp. 3409-3423.
@article{9861aedb942e47c7b85e7f1978bea468,
title = "The primary in vitro antitumor screening of 'half-mustard type' phenothiazines",
abstract = "The antitumor effects of 'half-mustard type' phenothiazines were studied on 57 different tumor cell lines, including leukemias, non-small lung cancer, colon, central nervous system, ovarian, renal, breast, and prostate cancer, as well as melanoma cell cultures. Alkyl-urea derivatives of phenothiazines displayed in vitro antitumor activity. The phenothiazine phthalimido derivatives (1-6) were not active on the majority of cancer cell cultures. In contrast, propyl-ureas (9, 11) were active against some leukemia cell types. Only two compounds with the butylene [(CH2)4] linker (10, 12) were active against non-small lung cancer cells. Compounds containing the propylene linker were less effective. On colon cancer lines, tumor cells from the central nervous system and on melanoma cells the same compounds were effective, however, having substituents at the 2-position of phenothiazine seems to be important. Surprisingly, the majority of ovarian cancer cell lines (except one type, IGROVI) and five of eight renal cancer lines were not sensitive to these phenothiazine derivatives. The two butylene linked phenothiazine ureas (10, 12) had moderate antiproliferative action on two renal cancer cell lines. The prostate cancer and some breast cancer cell lines were not sensitive. Nevertheless some breast cancer cell lines were apparently sensitive to CF3-substituted phenothiazine alkylureas. On the basis of these experiments one may postulate that in the case of insensitive cells an mdr-gene encoded multidrug resistance efflux pump is responsible for the resistance. The selectivity or organ cell specificity of the effective phenothiazines will be targeted for improvement in further studies, in order to avoid the general cytotoxic effects of 'half mustard type' phenothiazines.",
keywords = "Antitumor activity, Phenothiazines",
author = "Wuonola, {Mark A.} and Palfreyman, {Michael G.} and Noboru Motohashi and Masami Kawase and Sabit Gabay and J{\'a}nos Nacsa and J. Moln{\'a}r",
year = "1997",
month = "9",
language = "English",
volume = "17",
pages = "3409--3423",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "5 A",

}

TY - JOUR

T1 - The primary in vitro antitumor screening of 'half-mustard type' phenothiazines

AU - Wuonola, Mark A.

AU - Palfreyman, Michael G.

AU - Motohashi, Noboru

AU - Kawase, Masami

AU - Gabay, Sabit

AU - Nacsa, János

AU - Molnár, J.

PY - 1997/9

Y1 - 1997/9

N2 - The antitumor effects of 'half-mustard type' phenothiazines were studied on 57 different tumor cell lines, including leukemias, non-small lung cancer, colon, central nervous system, ovarian, renal, breast, and prostate cancer, as well as melanoma cell cultures. Alkyl-urea derivatives of phenothiazines displayed in vitro antitumor activity. The phenothiazine phthalimido derivatives (1-6) were not active on the majority of cancer cell cultures. In contrast, propyl-ureas (9, 11) were active against some leukemia cell types. Only two compounds with the butylene [(CH2)4] linker (10, 12) were active against non-small lung cancer cells. Compounds containing the propylene linker were less effective. On colon cancer lines, tumor cells from the central nervous system and on melanoma cells the same compounds were effective, however, having substituents at the 2-position of phenothiazine seems to be important. Surprisingly, the majority of ovarian cancer cell lines (except one type, IGROVI) and five of eight renal cancer lines were not sensitive to these phenothiazine derivatives. The two butylene linked phenothiazine ureas (10, 12) had moderate antiproliferative action on two renal cancer cell lines. The prostate cancer and some breast cancer cell lines were not sensitive. Nevertheless some breast cancer cell lines were apparently sensitive to CF3-substituted phenothiazine alkylureas. On the basis of these experiments one may postulate that in the case of insensitive cells an mdr-gene encoded multidrug resistance efflux pump is responsible for the resistance. The selectivity or organ cell specificity of the effective phenothiazines will be targeted for improvement in further studies, in order to avoid the general cytotoxic effects of 'half mustard type' phenothiazines.

AB - The antitumor effects of 'half-mustard type' phenothiazines were studied on 57 different tumor cell lines, including leukemias, non-small lung cancer, colon, central nervous system, ovarian, renal, breast, and prostate cancer, as well as melanoma cell cultures. Alkyl-urea derivatives of phenothiazines displayed in vitro antitumor activity. The phenothiazine phthalimido derivatives (1-6) were not active on the majority of cancer cell cultures. In contrast, propyl-ureas (9, 11) were active against some leukemia cell types. Only two compounds with the butylene [(CH2)4] linker (10, 12) were active against non-small lung cancer cells. Compounds containing the propylene linker were less effective. On colon cancer lines, tumor cells from the central nervous system and on melanoma cells the same compounds were effective, however, having substituents at the 2-position of phenothiazine seems to be important. Surprisingly, the majority of ovarian cancer cell lines (except one type, IGROVI) and five of eight renal cancer lines were not sensitive to these phenothiazine derivatives. The two butylene linked phenothiazine ureas (10, 12) had moderate antiproliferative action on two renal cancer cell lines. The prostate cancer and some breast cancer cell lines were not sensitive. Nevertheless some breast cancer cell lines were apparently sensitive to CF3-substituted phenothiazine alkylureas. On the basis of these experiments one may postulate that in the case of insensitive cells an mdr-gene encoded multidrug resistance efflux pump is responsible for the resistance. The selectivity or organ cell specificity of the effective phenothiazines will be targeted for improvement in further studies, in order to avoid the general cytotoxic effects of 'half mustard type' phenothiazines.

KW - Antitumor activity

KW - Phenothiazines

UR - http://www.scopus.com/inward/record.url?scp=0030775166&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030775166&partnerID=8YFLogxK

M3 - Article

C2 - 9413180

AN - SCOPUS:0030775166

VL - 17

SP - 3409

EP - 3423

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 5 A

ER -