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Development of biochemical modulators and application of the same with anticancer drugs is a current approach of modern cancer chemotherapy. We report the effect of two novel hydroxamic acid derivatives, viz. oxaly bis (N-phenyl) hydroxamic acid (OBPHA) and succinyl bis (N-phenyl) hydroxamic acid (SBPHA) on doxorubicin sensitivity and on P-glycoprotein (P-gp) in acetyl amino fluorene (AAF) induced preneoplastic hepatocytes in vitro. OBPHA increases doxorubicin sensitivity in AAF induced preneoplastic hepatocytes compared to normal hepatocytes. SBPHA, with an additional –CH2–CH2– group than OBPHA does not modulate the sensitivity of doxorubicin. The mechanism of action of OBPHA and SBPHA and their in vivo toxicity on male Swiss mice has been studied. OBPHA in combination with doxorubicin (i.e. OBPHA+doxorubicin) has higher antitumour activity compared to doxorubicin alone group; in consequence, OBPHA may decrease the dose related side effect of doxorubicin. [Copyright &y& Elsevier]