## 1 Introduction  
Camptothecin derivatives (CPTs) such as topotecan, irinotecan and belotecan are common chemotherapy agents that are used for the treatment of cancers. These therapeutic agents are used either as monotherapy or in combination with other anticancer drugs for the treatments of small cell lung cancer, metastatic colon and rectal carcinoma [1,2]. Belotecan was recently approved in South Korea for non-small-cell lung cancer and ovarian cancer [2]. The target of CPTs is topoisomerase I (TOP1) [3]. TOP1 plays an essential role during transcription, replication and repair of DNA by resolving helical duplex DNA topological problems. First, the enzyme forms a complex with double-strand DNA, a tyrosine residue at the TOP1 active site then introduces a single-strand break by catalysing the formation of a 3'-tyrosyl-phosphodiester bond, leading to the covalent linking of TOP1 and the 3'-phosphoryl end of the DNA. After rotation of the 5'-DNA end around the non-cleaved strand, the integrity of the DNA is restored, which is then followed by enzyme dissociation [4]. Binding of CPTs with the transient TOP1-DNA complex inhibits TOP1 dissociation, which subsequently leads to the formation of irreversible covalently-bound TOP1-DNA complexes, thus blocking replication and transcription [5]. The accumulation of DNA lesions halts cellular processes and results in cell death. Repair enzymes such as tyrosyl-DNA phosphodiesterase (Tdp1), 3'-flap endonucleases, and base excision repair (BER) complexes cleave covalent TOP1-DNA complexes, thus initiating DNA integrity recovery. The Tdp1 enzyme hydrolyses the 3'-phosphotyrosyl bond between single-strand DNA and TOP1, which is formed as a result of TOP1 hydrolysis catalysed by proteases. In addition, Tdp1 is involved in the elimination of other lesions at the 3'-end of DNA, for example, 3'-phosphoglycolate, and repair of apurinic/apyrimidinic sites generated by oxidative and free radical DNA damage [6; 7; 8]. Therefore, in the context of the molecular mechanism of CPTs, Tdp1 catalyses the dissociation of the TOP1-DNA complexes that are trapped by CPTs and; therefore, eliminating the therapeutic effect of TOP1 poisons. Moreover, Tdp1 activity was found to cause drug resistance of some cancer cell lines [9; 10; 11] and Tdp1 knockout cells were demonstrated to show increased sensitivity to CPT [12] and irinotecan [10]. Thus, enhancing anticancer the therapeutic effect can be achieved with the simultaneous administration of CPTs and Tdp1 inhibitors [13]. Furthermore, Tdp1 inhibition can lead to synergistic effect with anticancer agents with other mechanisms of action, including bleomycin and its derivatives as well as monofunctional alkylating agents or even radiotherapy [14; 15]. A wealth of Tdp1 inhibitors have been identified so far with various molecular scaffolds (see Figure 1) and potency down to nano-molar activity [16; 17; 18; 19; 20; 21; 22; 23; 24; 25; 26; 27; 28; 29; 30]. It is known that monoterene derivatives have various biological activities [41]. Interestingly, potent Tdp1 inhibitory activity was obtained for citral, citronellal and perillaldehyde derivatives of usnic acid, citronellal derivative **17** with IC\({}_{50}\) = 0.43 \(\upmu\)M) [34] and 7-hydroxycoumarin, most potent being **18** with IC\({}_{50}\) = 0.33 \(\upmu\)M, the structures are shown in Figure 2. Furthermore, derivative **18** had synergistic effect with CPT, **18** increasing CPT cytotoxicity eight-fold in the breast adenocarcinoma MCF-7 cell line [42]. Monoterpene derivatives of substituted anilines were found to be active at low micromolar concentrations (IC\({}_{50}\) = 1.29 \(\upmu\)M) for **19** and for **20** (IC\({}_{50}\) = 0.79 \(\upmu\)M) (Figure 2) [43]. Additionally, potent inhibitory activity was found for derivatives containing adamantane. Bile acid amide **21** inhibited Tdp1 with IC\({}_{50}\) = 0.47 \(\upmu\)M [44], whilst octahydro-2\(H\)-chromen-4-ol derivative **22** IC\({}_{50}\) was 1.24 \(\upmu\)M (see Figure 2) [45].