Chemical structure and tumor type specificity of "half-mustard type" phenothiazines.
The antiproliferative activity of six "half-mustard type" phenothiazines against a total of 54 tumor cell lines: 4 leukemia, 9 non-small-cell lung, 7 colon-, 5 CNS-, 8 melanoma, 6 ovarian-, 8 renal-, 1 prostate and 6 breast cancer was determined by NCI-Information Intensive-Approach. The C-2 position of phenothiazines were substituted with H, Cl and CF3 groups. The half-mustard and ring system was linked either by a propylene or a butylene bridge. Colon-cancer cell showed the highest sensitivity against "half-mustard type" phenothiazines, followed by leukemia, melanoma, prostate-, CNS-, breast-, lung-, renal and ovarian cancer cells. These data suggest the "cancer-type-specific" antitumor action of "half-mustard type" phenothiazines.
Motohashi
N
N
Department of Medicinal Chemistry, Meiji Pharmaceutical University, Tokyo, Japan. motohasi@my-pharm.ac.jp
Kurihara
T
T
Sakagami
H
H
Szabo
D
D
Csuri
K
K
Molnár
J
J
D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology; D002277:Carcinoma / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000473:pathology; D003110:Colonic Neoplasms / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology; D007938:Leukemia / Q000473:pathology; D008175:Lung Neoplasms / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000473:pathology; D015394:Molecular Structure; D009150:Mustard Compounds / Q000737:chemistry* / Q000494:pharmacology; D009928:Organ Specificity; D010051:Ovarian Neoplasms / Q000473:pathology; D010640:Phenothiazines / Q000737:chemistry* / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000473:pathology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D018906:Antineoplastic Agents, Alkylating; D009150:Mustard Compounds; D010640:Phenothiazines