Research progress on natural products with "selective cytotoxicity" / 中草药

At present, anti-tumor chemotherapy drugs used in clinic commonly have serious side effects on normal tissues. Although targeted and antibody anti-tumor drugs have made progress in clinic, the high medical cost makes it difficult for many patients to afford. To find effective and low toxic anti-tumor agents without increasing medical cost, it is still the challenges of current research. Based on the natural products with selective cytotoxicity, we aimed to summarize the research progress, provide ideas for the basic research and clinical development of antitumor agents.

Cytotoxic and anticancer properties of the Malaysian mangrove pit viper (Trimeresurus purpureomaculatus) venom and its disintegrin (purpureomaculin)

The Asiatic pit vipers from the Trimeresurus complex are medically important venomous snakes. These pit vipers are often associated with snakebite that leads to fatal coagulopathy and tissue necrosis. The cytotoxic venoms of Trimeresurus spp.; however, hold great potential for the development of peptide-based anticancer drugs. Methods: This study investigated the cytotoxic effect of the venom from Trimeresurus purpureomaculatus, the mangrove pit viper (also known as shore pit viper) which is native in Malaysia, across a panel of human cancer cell lines from breast, lung, colon and prostate as well as the corresponding normal cell lines of each tissue. Results: The venom exhibited dose-dependent cytotoxic activities on all cell lines tested, with median inhibition concentrations (IC50) ranging from 0.42 to 6.98 µg/mL. The venom has a high selectivity index (SI = 14.54) on breast cancer cell line (MCF7), indicating that it is significantly more cytotoxic toward the cancer than to normal cell lines. Furthermore, the venom was fractionated using C18 reversed-phase high-performance liquid chromatography and the anticancer effect of each protein fraction was examined. Fraction 1 that contains a hydrophilic low molecular weight (approximately 7.5 kDa) protein was found to be the most cytotoxic and selective toward the breast cancer cell line (MCF7). The protein was identified using liquid chromatography-tandem mass spectrometry as a venom disintegrin, termed purpureomaculin in this study. Conclusion: Taken together, the findings revealed the potent and selective cytotoxicity of a disintegrin protein isolated from the Malaysian T. purpureomaculatus venom and suggested its anticancer potential in drug discovery.(AU)

New aporphine alkaloids with selective cytotoxicity against glioma stem cells from Thalictrum foetidum / 中国天然药物

Seven new isoquinoline alkaloids, 9-(2'-formyl-5', 6'-dimethoxyphenoxy)-1, 2, 3, 10-tetramethoxy dehydroaporphine (1), 9-(2'-formyl-5', 6'-dimethoxyphenoxy)-1, 2, 3, 10-tetramethoxy oxoaporphine (2), 3-methoxy-2'-formyl oxohernandalin (3), (-)-9-(2'-methoxycarbonyl-5', 6'-dimethoxyphenoxy)-1, 2, 3, 10-tetramethoxy aporphine (4), (-)-2'-methoxycarbonyl thaliadin (5), (-)-9-(2'-methoxyethyl-5', 6'-dimethoxyphenoxy)-1, 2, 3, 10-tetramethoxy aporphine (6), (-)-3-methoxy hydroxyhernandalinol (7), together with six known isoquinoline alkaloids (8-13) were isolated from the roots of Thalictrum foetidum. Their structures were elucidated by extensive spectroscopic measurements. Compounds 1 and 2 showed significant selective cytotoxicity against glioma stem cells (GSC-3 and GSC-18) with IC values ranging from 2.36 to 5.37 μg·mL.

Selective Cytotoxicity of Novel Platinum (II) Coordination Complexes on Human Bladder Cancer Cell-Lines and Normal Kidney Cells

Cisplatin is often effective in cancer treatment, but its clinical use is limited because of its nephrotoxicity. We have synthesized new platinum (II) coordination complexes (PC-1 & PC-2) containing trans-l and cis-1, 2-diaminocyclohexane (DACH) as carrier ligands and L-3 -phenyllactic acid (PLA) as a leaving group with the aim of reducing nephrotoxicity but maintaining its anticancer activity. In this study, new platinum (II) complex compounds were evaluated for selective cytotoxicity on cancer cell-lines and normal kidney cells. The new platinum complexes have demonstrated high efficacy in the cytotoxicity against human bladder carcinoma cell-lines (T-24/HT-1376). The cytotoxicity of these compounds against rabbit proximal renal tubular cells and human renal cortical tissues, was determined by MTT assay, the [3H]-thymidine uptake and glucose consumption test, and found to be quite less than those of cisplatin. Based on our results, these novel platinum compounds appear to be valuable lead compounds with high efficacy and low nephrotoxicity.

Selective Cytotoxicity of the New Platnum ( 2 ) Complexes on Human Gastric Cancer Cell - lines and Normal Kidney Cells / 대한암학회지

PURPOSE: Platinum coordination complex (cisplatin) has been currently used as one of the most effective compound in the treatment of various solid tumors. However, its use has been limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program has been aimed at developing drugs capable of diminishing toxicity and selective cytotoxicity. MATERIALS AND METHODS: A new series of highly water soluble platinum (II) complexes Pt (II) [1,3-Bis (phenylthio) propane) (trans-l-1,2-diaminocyclohexane) (PC-1) and Pt (II) [1,3-Bis-(phenylthio) (propane)]-1,2-diaminocyclohexane (PC-2) were synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (.IR), ""C-nuclear magnetic resonance (NMR)]. In vitro antitumor activity and nephrotoxi -cities of new Pt (II) complexes were tested against MKN-45 human gastric cancer cell- lines and normal kidney cells using colorimetric MTT[3-(4,5-dimethyl thiazol-2-yl)-2,5- diphenyl tetrazolium bromide] assay for cell survival and proliferation. RESULTS: PC-1 showed activity against MKN-45/P and MKN-45/CDDP human gastric adenocarcinoma cells, and the antitumor activity of this compound was comparable or superior to that of PC-2 and cisplatin. The nephrotoxicity of PC-1 and PC-2 were found quite less than that of cisplatin using MTT, [H] thymidine uptake and glucose consumption tests in rabbit proximal tubule cells, human kidney cortical cells and human renal cortical tissues. CONCLUSION: Based on these results, this novel platinum (II) complex compound (PC-1) represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low nephrotoxicity.

Selective cytotoxicity of a novel platinum (II) coordination complex on human gastric cancer cell lines and normal kidney cells

We have synthesized novel platinum (II) coordination complex containing cis-1,2-diaminocyclohexane (DACH) as a carrier ligand and 1,2-bis(diphenylphosphino)ethane (DPPE) as leaving group. Furthermore, nitrate was added to improve the water-solubility. A new series of (Pt(cis-DACH)(DPPE)) cntdot 2NO3 (PC) was evaluated its antitumor activity on various MKN-45 human gastric adenocarcinoma cell-lines and normal primary cultured kidney cells. The new platinum complex demonstrated high efficacy in the cytotoxicity on MKN-45 cell-lines as well as adriamycin-resistant (MKN-45/ADR) and cisplatin-resistant (MKN-45/CDDP) cells. The cytotoxicities of PC were found quite less than those of cisplatin in rabbit proximal renal tubular cells, human renal cortical cells and human renal cortical tissues using MTT assay, (3H)-thymidine uptake and glucose consumption tests. Based on these results, this novel platinum (II) coordination complex, was considered as better a valuable lead for improving antitumor activities with low nephrotoxicities in the development of a new clinically available anticancer chemotherapeutic agents.