TABLE 1.
Several compounds affecting SDH activity have been tested for their anticancer properties, IR injury and anti-inflammatory effects.
| Compound | Target | Mechanism of action | Functions in cancer | Diseases | Ref |
|---|---|---|---|---|---|
| α-TOS | SDHC&SDHD | Interacting with both proximal (Qp) and distal (Qd) UbQ sites | Inducing cancer cells apoptosis via ROS | Colon cancer, breast cancer, prostate cancer, lung cancer, mesotheliomas, melanomas | Neuzil et al. (2001); Malafa et al. (2002); Weber et al. (2002); Kline et al. (2004); Tomasetti et al. (2004); Quin et al. (2005); Stapelberg et al. (2005); Malafa et al. (2006); Neuzil et al. (2006); Wang et al. (2007); Dong et al. (2008); Dong et al. (2009) |
| MitoVES | SDH | Qp site | Inducing cancer cells apoptosis via ROS | Breast carcinoma, colon cancer | Dong et al. (2011a); Dong et al. (2011b) |
| 3-BP | HK | Causing cancer cells death by the fast depletion of ATP | Advanced cancers Fibrolamellar | Ko et al. (2004); Mathupala et al. (2006); Pereira da Silva et al. (2009); Ko et al. (2012); Pedersen (2012); Rodrigues-Ferreira et al. (2012) | |
| SDH | Inhibiting SDH activity | HCC | |||
| 3NP | SDH | Inducing ROS and apoptosis | Neuroblastoma, PD, HD | Huang et al. (2006); Gomez-Lazaro et al. (2007) | |
| TTFA | SDHC&SDHD | Interfering with the UbQ-binding site | Inducing apoptosis and trigger superoxide/hydrogen peroxide and increase Ca2+ levels | Leishmania spp infection | Mehta and Shaha (2004) |
| Troglitazone | SDH | Interfering with SDH activity; Inducing cancer cell cycle arrest, differentiation, and apoptosis | Liposarcomas, prostate cancer, colorectal cancer | Demetri et al. (1999); Hisatake et al. (2000); Gupta et al. (2001); Kopelovich et al. (2002); Koeffler (2003); Soller et al. (2007); Wei et al. (2009) | |
| Atpenins | SDH | UbQ | Interfering with the UbQ site, prevents reduction of UbQ and induces ROS | IR injury | Miyadera et al. (2003); Horsefield et al. (2006); Wojtovich and Brookes (2009); Ralph et al. (2011); Quinlan et al. (2012) |
| LND | SDHC&SDHD | Transferring electrons from the iron sulfur clusters to ubiquinone | Inducing ROS and cancer cell death | Melanoma | Guo et al. (2016) |
| DT-010 | Complex II | Inducing ROS generation, cytotoxicity and promoting cell arrest | Breast cancer | Wang et al. (2016) | |
| Chrysin | Complex II | Inhibiting SDH activity and increasing ROS generation associated to apoptosis | CLL | Salimi et al. (2017) | |
| Dimethyl malonate | SDH | Inducing ROS with calcium dysregulation and ATP depletion via inhibiting SDH | IR injury (heart attack, ischemic stroke), tissue damage, and inflammation | Chouchani et al. (2014); Xu et al. (2018); Kula-Alwar et al. (2019) | |
| Ginsenoside Rb1 | Complex I | Inhibiting ROS production | Myocardial IR injury | Jiang et al. (2021) | |
| 3-BrPA | SDH | Decreasing SDH expression; Cancer cell cycle arrest and apoptotic induction via suppressing aerobic glycolysis | HCC, PC, endometrial cancer, Staphylococcus aureus infection; metastatic prostate cancer | Liu et al. (2009); Pereira da Silva et al. (2009); Cardaci et al. (2012); Birsoy et al. (2013); Byrne et al. (2014); Chapiro et al. (2014); Yadav et al. (2017); Abdel-Wahab et al. (2019); Pichla et al. (2019); Visca et al. (2019); Sun et al. (2020); Yu et al. (2021) | |
| Compound 968, CB-839 and JQ1 | Succinate | Inhibiting glutaminase 1 and BET | Suppressing the growth of the SDHB knockout cells | Colon cancer | Kitazawa et al. (2017); Godel et al. (2021) |
α-TOS, α-tocopheryl succinate; SDH, succinate dehydrogenase; ROS, reactive oxygen species; MitoVES, mitochondrially targeted vitamin E succinate; 3-BP, 3-Bromopyruvate; HK, hexokinase; ATP, adenosine triphosphate; 3NP, 3-nitropropionic acid; TTFA, thenoyltrifluoroacetone; LND, lonidamine; DT-010, a conjugate of danshensu (DSS) and tetramethylpyrazine (TMP); 3-BrPA, 3-bromopyruvate; IR, injury, ischemia/reperfusion injury; PD, Parkinson’s disease; HD, Huntington’s disease; HCC, hepatocellular carcinoma; PC, pancreatic cancer; BET, bromodomain and extra-terminal; CLL, chronic lymphocytic leukemia; Compound 968 and CB-839, glutaminase 1 inhibitor; JQ1, a BET, inhibitor.