Table 3 Details of calculated toxicity risk parameters for compound P-902 and control drug topotecan.

From: 3D-QSAR studies on Maslinic acid analogs for Anticancer activity against Breast Cancer cell line MCF-7

Properties P-902 Topotecan
Maximum recommended therapeutic dose, administered orally Below 3.16 mg/kg/day Above 3.16 mg/kg/day
Estrogen receptor (rats) Non-toxic Toxic
Quantitative measure of estrogen receptor toxicity in rats Non-toxic 4.3531
Androgen receptor toxicity Toxic Toxic
Quantitative measure of androgen receptor toxicity in rats 0.037 0.0599
Allergenic skin sensitization (mice) No sensitization No sensitization
Allergenic respiratory sensitization in rat No sensitization No sensitization
Fathead minnow lethal toxicity after 96 hours of exposure 0.31 mg/L 1.5 mg/L
Daphnia magna (water flea) lethal toxicity after 48 hours of exposure 0.893 mg/L 0.549 mg/L
Bio concentration factor 3.781 4.688
Biodegradation No No
Likelihood of the hERG potassium channel inhibition in human No (95%) No
Affinity towards hERG K+ channel and potential for cardiac toxicity 5.060 mol/L 5.24 mol/L
LD50 for lethal rat acute toxicity 204.531 mg/kg 782.92 mg/kg
Tumorogenic dose, rat 84.385 mg/kg/day 9.94 mg/kg/day
Tumorogenic dose, mice 381.422 mg/kg/day 74.25 mg/kg/day
Triggering the mutagenic chromosomal aberrations Non-toxic Toxic
Hepatotoxicity levels of Alkaline Phosphatase enzyme Elevated Elevated
levels of GGT enzyme Normal Normal
levels of LDH enzyme Elevated Normal
levels of SGOT enzyme Normal Elevated
levels of SGPT enzyme Normal Normal
Causing phospholipidosis Non-toxic Non-toxic
Reproductive/developmental toxicity Non-toxic Non-toxic
Mutagenicity (pure compound) TA97 and/or TA1537 strains of S. typhimurium Negative Positive
TA98 strain of S. typhimurium Negative Negative
TA100 strain of S. typhimurium Negative Negative
S. typhimurium and/or WP2 uvrA strain of E. coli Negative Positive
TA1535 strain of S. typhimurium Negative Negative
Mutagenicity (microsomal rat liver metabolites) TA97 and/or TA1537 strains of S. typhimurium Negative Positive
TA98 strain of S. typhimurium Negative Negative
TA100 strain of S. typhimurium Negative Negative
TA102 strain of S. typhimurium Negative Negative
TA1535 strain of S. typhimurium Negative Negative
  1. Abbreviations: LD50, lethal dose 50%; hERG, human Ether-a-go-go-Related Gene; SGOT, serum glutamic oxaloacetic transaminase; SGPT, serum glutamate-pyruvate transaminase; GGT, gamma-glutamyl transpeptidase; LDH, lactate dehydrogenase.