Evaluation of antitumor efficacy and toxicity of novel 6-nitro-2-(3-chloropropyl)-1H-benz[de]isoquinoline-1,3-dione in vivo in mouse.

Aim: This study was aimed to assess the in vivo anti-tumoral potency of the novel 6-nitro-2-(3-chloropropyl)-1H-benz[de]isoquinoline-1,3-dione [Compound 1] that has earlier demonstrated excellent cytotoxicity in 15 out of 17 human tumor cell lines tested.

Materials And Methods: Two murine tumors namely Sarcoma-180 (S-180) and Ehrlich ascites carcinoma (EAC) were used to measure its in vivo anti-tumor activity through the increase in median survival times (MST) of drug treated (T) over untreated control (C) mice. Drug-induced toxicity in respect of hematological parameters, femoral bone marrow and splenic cellularity as well as biochemical parameters and histopathology of liver and kidney were assessed in vivo in normal and S-180 bearing mice sequentially on days 9, 14 and 19 following drug treatment at the optimum dose of 60 mg/kg administered from day 1 to 7.

6-Nitro-2-(3-hydroxypropyl)-1H-benz[de]isoquinoline-1,3-dione, a potent antitumor agent, induces cell cycle arrest and apoptosis.

Background: Anticancer activities of several substituted naphthalimides (1H-benz[de]isoquinoline-1,3-diones) are well documented. Some of them have undergone Phase I-II clinical trials. Presently a series of ten N-(hydroxyalkyl) naphthalimides (compounds 1a-j) were evaluated as antitumor agents.

Antitumor efficacy and apoptotic activity of substituted chloroalkyl 1H-benz[de]isoquinoline-1,3-diones: a new class of potential antineoplastic agents.

A series of ten chloroalkyl 1H-benz[de]isoquinoline-1,3-diones (naphthalimides) were synthesized and evaluated for antitumor activity. Amongst them, new compounds 2d and 2i carrying a 6-NO(2) substituent in the aromatic portion of the molecule possessed significant antineoplastic activity. The most active compound 2i had elicited significant cytotoxicity in 15 human tumor cell lines namely Leukemia: MOLT-4, HL-60; Lymphoma: U-937; Colon: 502713, HT-29, SW-620, HCT-15, COLO-205; Liver: Hep-2; Prostate DU-145, PC-3; Breast: MCF-7; Neuroblastoma: IMR-32, SK-N-SH and Ovary: OVCAR-5 out of the 17 cell lines screened.

Neem leaf glycoprotein matures myeloid derived dendritic cells and optimizes anti-tumor T cell functions.

In an objective to find out an effective, nontoxic dendritic cell (DC) maturating agent for human use, CD14(+) monocytes were differentiated with GMCSF/IL-4 and matured with neem leaf glycoprotein (NLGP). NLGP matured DCs (NLGP-DCs) show upregulated expression of CD83, CD80, CD86, CD40 and MHCs, in a comparable extent of control, LPS. NLGP-DCs secrete high amount of IL-12p70 with low IL-10.

Evaluation of fluoren-NU as a novel antitumor agent.

A new nitrososourea derivative, namely fluoren-NU, 3-[2-(3-(2-chloroethyl)-3-nitrosouriedo}ethyl]-spiro[5,9'-fluorenyl]imidazolidine-2,4-dione (compound 2e), was synthesized from 3-(2-bromoethyl)-spiro [5,9'-fluorenyl]imidazolidine-2,4-dione via a four-step synthetic procedure. Its chemical alkylating activity was assessed by coupling with 4-(4-nitrobenzyl)pyridine. In vitro screening in six human tumor cell lines, namely SK-N-SH CNS, IMR-32 neuroblastoma, A549 lung, DU-145 prostate, HL-60 leukemia, and U-937 lymphoma, revealed its significant cytotoxicity in SK-N-SH.

Synthesis and evaluation of ethylnitrosoureas of substituted naphthalimides as anticancer compounds.

Four new ethylnitrosourea derivatives of substituted naphthalimides 3a-d have been synthesized from the respective N-(2-ethylamino) naphthalimides. Their chemical alkylating activity compared with the clinical drug CCNU and an experimental compound Mitonafide indicated that they possess lower alkylating activity than CCNU and comparable activity with the latter. Their anti-tumor efficacies were assessed in vivo in two murine ascites tumors namely Sarcoma-180 (S-180) and Ehrlich ascites carcinoma (EAC) by measuring the increase in median survival times (MST) of drug treated (T) over untreated control (C) mice.

Antitumor activity of Nitronaphthal-NU, a novel mixed-function agent.

Nitronaphthal-NU (Compound 1) was synthesized as a mixed-function antitumor agent based on the structures of the clinical drug CCNU and experimental compound Mitonafide. In vitro screening in four human tumor cell lines namely SNB-78 CNS, HOP-62 Lung, T47D Breast and SiHa - cervix revealed significant cytotoxicity in the former two cell lines much greater than CCNU and comparable to Mitonafide used as standards. In vivo antitumoral potency assessed in the murine ascites tumors Sarcoma-180 (S-180) and Ehrlich ascites carcinoma (EAC) by measuring the increase in median survival times of drug treated (T) over untreated control (C) mice, revealed highly significant (p<0.

Separation methods of quinonoid constituents of plants used in Oriental traditional medicines.

Analysis of molecular constituents of traditional Oriental medicines has acquired a fresh perspective in view of a surge in interest in the consumption of herbal prescriptions all over the world. Several of them contain quinonoid compounds, and the long-standing therapeutic applications of these herbs have been vindicated, to some extent, through recent studies on the significant pharmacological properties of these compounds. In fact, the bioactive quinonoids and their analogues often serve as the 'marker' constituents of the respective plants of major commercial importance.

Liquid chromatographic separation of derivatives of diospyrin, a bioactive bisnaphthoquinonoid plant-product, and analogous naphthyl compounds.

Isocratic reversed-phase liquid chromatography (LC) method was developed using acetonitrile and water for the determination of diospyrin, a pharmacologically important bisnaphthoquinonoid plant-product. The method was validated for precision, accuracy and reproducibility, and was found to be linear over the concentration range of 1-1000 microg/ml; the limits of detection and quantitation were 8 and 20 ng, respectively. The technique was used to determine the amount of diospyrin in plant extracts from four climatic regions in India.

Response of Cervical Intra-epithelial Lesions to Vitamin E Supplementation - A Preliminary Report.

Carcinoma of the uterine cervix is preceded by well characterized pre-cancerous lesions which if left untreated may progress to invasive carcinoma. In the present study women in the age group of 35-55 years with cervical intraepithelial lesions (CIN I & II) were treated with vitamin E and advised to come for follow up after every three months for one year. This preliminary report shows vitamin E can restrict and regress CIN I & II lesions with elevation in circulating vitamin E levels.