Comparison of in vivo and in vitro drug sensitivities of Lewis lung carcinoma and P388 leukaemia to analogues of Amsacrine

DNA-Directed Alkylating Agents. 7. Synthesis, DNA Interaction, and Antitumor Activity of Bis(hydroxymethyl)- and Bis(carbamate)-Substituted Pyrrolizines and Imidazoles

“…Cytotoxicity Assays . These were carried out as previously described . IC 50 values were determined with log-phase cultures in 96-well microtiter plates, with drug present throughout the growth period (72 h).…”

“…These were carried out as previously described. 28 IC50 values were determined with log-phase cultures in 96-well microtiter plates, with drug present throughout the growth period (72 h). The IC50 values are the average of at least two consistent and independent determinations, calculated as the nominal drug concentration needed to reduce the cell density to 50% of control values.…”

DNA-Directed Alkylating Agents. 7. Synthesis, DNA Interaction, and Antitumor Activity of Bis(hydroxymethyl)- and Bis(carbamate)-Substituted Pyrrolizines and Imidazoles

“…Cytotoxicity Assays . These were carried out as previously described . IC 50 values were determined with log-phase cultures in 96-well microtiter plates, with drug present throughout the growth period (72 h).…”

“…These were carried out as previously described. 28 IC50 values were determined with log-phase cultures in 96-well microtiter plates, with drug present throughout the growth period (72 h). The IC50 values are the average of at least two consistent and independent determinations, calculated as the nominal drug concentration needed to reduce the cell density to 50% of control values.…”

DNA-directed alkylating agents. 4. 4-Anilinoquinoline-based minor groove directed aniline mustards

“…The above compound (25) (4.3 g, 15.8 mmol) was hydrogenated over 10% Pd/C in MeOH, filtered, and evaporated to dryness. The resulting crude amide (26) was suspended in 1 N aqueous AcOH (30 mL), and the stirred suspension was treated with 2X1 mL portions of oxirane over a 24-h period. The mixture was then concentrated, and the resulting gum was partitioned between saturated NaHC03 solution and CH2C12.…”

In vitro screening of crude extracts and pure metabolites obtained from marine invertebrates for the treatment of breast cancer

“…Differences in relative chemosensitivities between cell lines were maintained when comparing the MTT and HTCFA assays (20). Other experiments comparing in vitro chemosensitivities of leukemia cell lines with carcinoma cell lines against a panel of cytotoxic agents has demonstrated that carcinomacell lines tend to be more chemoresistant than leukemic cell lines, especially when exposed to DNA binding drugs(4,52,115). These results suggest that the refractoriness of carcinomas as compared with leukemias is due to inherent resistance of the tumor cells themselves.…”

“…A knowledge of the potency of the test compound in vitro may provide a reference point on which to base in vivo drug dosages (122). The basis of all in vitro chemosensitivity assays is the hypothesis that response in vivo is determined by the inherent chemosensitivity of the cells in vitro.Experimental evidence has demonstrated that this is not always the case and that other factors determine tumor responses in vivo(4,122). A study by Phillips et a/ (122).…”

DNA-Directed Alkylating Agents. 7. Synthesis, DNA Interaction, and Antitumor Activity of Bis(hydroxymethyl)- and Bis(carbamate)-Substituted Pyrrolizines and Imidazoles

“…Cytotoxicity Assays . These were carried out as previously described . IC 50 values were determined with log-phase cultures in 96-well microtiter plates, with drug present throughout the growth period (72 h).…”

“…These were carried out as previously described. 28 IC50 values were determined with log-phase cultures in 96-well microtiter plates, with drug present throughout the growth period (72 h). The IC50 values are the average of at least two consistent and independent determinations, calculated as the nominal drug concentration needed to reduce the cell density to 50% of control values.…”

DNA-directed alkylating agents. 4. 4-Anilinoquinoline-based minor groove directed aniline mustards

“…The above compound (25) (4.3 g, 15.8 mmol) was hydrogenated over 10% Pd/C in MeOH, filtered, and evaporated to dryness. The resulting crude amide (26) was suspended in 1 N aqueous AcOH (30 mL), and the stirred suspension was treated with 2X1 mL portions of oxirane over a 24-h period. The mixture was then concentrated, and the resulting gum was partitioned between saturated NaHC03 solution and CH2C12.…”

In vitro screening of crude extracts and pure metabolites obtained from marine invertebrates for the treatment of breast cancer

“…Differences in relative chemosensitivities between cell lines were maintained when comparing the MTT and HTCFA assays (20). Other experiments comparing in vitro chemosensitivities of leukemia cell lines with carcinoma cell lines against a panel of cytotoxic agents has demonstrated that carcinomacell lines tend to be more chemoresistant than leukemic cell lines, especially when exposed to DNA binding drugs(4,52,115). These results suggest that the refractoriness of carcinomas as compared with leukemias is due to inherent resistance of the tumor cells themselves.…”

“…A knowledge of the potency of the test compound in vitro may provide a reference point on which to base in vivo drug dosages (122). The basis of all in vitro chemosensitivity assays is the hypothesis that response in vivo is determined by the inherent chemosensitivity of the cells in vitro.Experimental evidence has demonstrated that this is not always the case and that other factors determine tumor responses in vivo(4,122). A study by Phillips et a/ (122).…”

DNA-Directed Alkylating Agents. 7. Synthesis, DNA Interaction, and Antitumor Activity of Bis(hydroxymethyl)- and Bis(carbamate)-Substituted Pyrrolizines and Imidazoles

“…Cytotoxicity Assays . These were carried out as previously described . IC 50 values were determined with log-phase cultures in 96-well microtiter plates, with drug present throughout the growth period (72 h).…”

“…These were carried out as previously described. 28 IC50 values were determined with log-phase cultures in 96-well microtiter plates, with drug present throughout the growth period (72 h). The IC50 values are the average of at least two consistent and independent determinations, calculated as the nominal drug concentration needed to reduce the cell density to 50% of control values.…”

DNA-directed alkylating agents. 4. 4-Anilinoquinoline-based minor groove directed aniline mustards

“…The above compound (25) (4.3 g, 15.8 mmol) was hydrogenated over 10% Pd/C in MeOH, filtered, and evaporated to dryness. The resulting crude amide (26) was suspended in 1 N aqueous AcOH (30 mL), and the stirred suspension was treated with 2X1 mL portions of oxirane over a 24-h period. The mixture was then concentrated, and the resulting gum was partitioned between saturated NaHC03 solution and CH2C12.…”

In vitro screening of crude extracts and pure metabolites obtained from marine invertebrates for the treatment of breast cancer

“…Differences in relative chemosensitivities between cell lines were maintained when comparing the MTT and HTCFA assays (20). Other experiments comparing in vitro chemosensitivities of leukemia cell lines with carcinoma cell lines against a panel of cytotoxic agents has demonstrated that carcinomacell lines tend to be more chemoresistant than leukemic cell lines, especially when exposed to DNA binding drugs(4,52,115). These results suggest that the refractoriness of carcinomas as compared with leukemias is due to inherent resistance of the tumor cells themselves.…”

“…A knowledge of the potency of the test compound in vitro may provide a reference point on which to base in vivo drug dosages (122). The basis of all in vitro chemosensitivity assays is the hypothesis that response in vivo is determined by the inherent chemosensitivity of the cells in vitro.Experimental evidence has demonstrated that this is not always the case and that other factors determine tumor responses in vivo(4,122). A study by Phillips et a/ (122).…”