Preclinical antitumor activity of ethyldeshydroxysparsomycin in combination with cisplatin

Hofs, H. P.; Wagener, D.J.T.; Valk-Bakker, V. de; Rennes, Helga van; Vos, Dick de; Doesburg, W.H.; Ottenheijm, H. C. J.; Grip, W.J. de

doi:10.1007/bf02614216

Cited by 5 publications

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“…After the discovery of the anticancer activity of cisplatin Platinum based drugs have played a vital role in the treatment of cancers by chemical agents. Cisplatin cis-diaminedichloroplatinum (II) (DDP) has a wide variety of application in cancer chemotherapy [ 2 - 5 ]. Although cisplatin has been found to shrink the tumor burden it also results in toxicity by decreasing the body weight [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Histological vis – a – vis biochemical assessment on the toxic level and antineoplastic efficacy of a synthetic drug Pt – ATP on experimental animal models

Pal

Sadhu

Patra

et al. 2008

J Exp Clin Cancer Res

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BackgroundCisplatin, a platinum based anticancer drug has played a vital role in the treatment of cancers by chemical agents, but in view of the serious toxicity including nephrotoxicity of cisplatin, various other platinum based drugs have been synthesized and screened to overcome its toxicity. A Pt-ATP compound was prepared in our laboratory hoping to have reduced or no toxicity along with the potentiality of reducing neoplasm growth.MethodsA Pt-ATP compound was prepared. It was first screened for its antineoplastic efficacy. Confirming that, subsequent experiments were carried on to test its toxicity on animals, viz. Albino Swiss mice. The animals were randomly divided into four sets – Set I: Erhlich Ascites Carcinoma (EAC) challenged mice; Set II: Normal mice; Set III: Drug treated mice, Set IVA Cisplatin (CDDP) treated mice, Set IV B EAC challenged Cisplatin treated mice. Set I was used to test antineoplasticity of the drug, Set II and Set III for studying drug toxicity and Set IV was treated with CDDP. Set II was used as a control. Animals were sacrificed after 5 days, 10 days 15 days and 20 days of drug administration on the 6th, 11th, 16th and 21st days respectively for Set I, II and III. Set IVA was sacrificed only on the 16th day and Set IV B on 6th and 11th days. For Set I only tumor cell count and packed cell volume (PCV) of tumor cells were recorded. For Set II and III, aspartate aminotransferase (AST), alanine aminotransferase (ALT) assays were done using serum while blood creatinine and creatine were assayed from blood filtrate. For cytotoxicity assessment liver, spleen and kidney tissues were collected and subjected to scanning electron microscopy (SEM) after extensive treatment. Set IV A was only studied for the biochemical parameters viz. aspartate aminotransferase (AST), alanine aminotransferase (ALT) assays were done using serum while blood creatinine and creatine were assayed from blood filtrate. Set IV B was studied for tumor cell count after treatment with CDDP for 10 days.ResultsOur comparative studies with normal and drug treated animals reveal that the drug does not affect the body weight of the drug treated animals significantly. The biochemical parameters like ALT and AST levels are also within normal limits which rules out hepatotoxicity. The detailed histological studies by SEM reveal that the hepatic, kidney and spleen tissues are not adversely affected by the drug. Comparison of biochemical parameters with the CDDP treated animals show that Pt-ATP is not at all toxic like the CDDP. The Kaplan-Meier analysis of the survival data of Set I has shown promising results with a significance of p < 0.0001.ConclusionSet I results are promising and indicating antineoplastic efficacy of the synthesized drug with increased life span of the animals. Biochemical analysis, hematological and SEM studies revealed that the drug was neither nephrotoxic nor hepato-spleeno-toxic under the experimental set up.

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Section: Introductionmentioning

confidence: 99%

Histological vis – a – vis biochemical assessment on the toxic level and antineoplastic efficacy of a synthetic drug Pt – ATP on experimental animal models

Pal

Sadhu

Patra

et al. 2008

J Exp Clin Cancer Res

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“…An extended study with 60 (5 mg/kg) with cisdiamminedichloroplatinum(II) (CDDP) (3 mg/kg) produced 80% cures in mice treated with L1210 leukemia cells. 63,64 Further research established that 60 decreased the cellular protein levels and the overall glutathione S transferase activity in opposition to cisplatin which has detoxifying effects. 65 As a single agent, when administered i.p.…”

Section: Biology and Sar Of Sparsomycinmentioning

confidence: 99%

Sparsomycin – a Review and Re-assessment

Cordell¹,

Daley²

2022

HETEROCYCLES

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The chemistry, biology, and biosynthesis of the microbial alkaloid sparsomycin (1) are summarized and re-assessed to identify future research initiatives for this biologically significant metabolite. INTRODUCTIONOne of the underexplored facets of natural product chemistry and biology is the further exploration of "old" bioactive metabolites to fill-in important gaps in basic knowledge, or to explore new or underappreciated applications given the contemporary opportunities in biological assessment and mechanistic understanding.The microbial alkaloid sparsomycin is one such example based on its anticancer, antimicrobial, insecticidal, and tRNA:mRNA translocation activities. Sparsomycin was first reported in 1962 by researchers at the Upjohn Co., Kalamazoo, MI, as a cytotoxic and antitumor alkaloid from the soil microorganism Streptomyces sparsogenes var. sparsogenes, 1,2 where it co-occurred with tubercidin. 2 Several years later, the molecular formula was corrected to C13H19N3O5S2 and the planar structure 1 determined through spectral interpretation and chemical degradation. 3,4 Additional isolations of 1 are rare. For example, a soil sample acquired in Kyoto, Japan, Streptomyces cuspidosporus was isolated and culturing yielded sparsomycin (1) and the antitubercular alkaloid tubercidin. 5 A water sample from the Nile River afforded 1 from Streptomyces violaceusniger AZ-NIOFD, 6 and a derivative of sparsomycin with a unit of H2O added was reported from a soil sample of Pseudomonas aeruginosa AZ-SH-B8 collected in the Sharqia Governorate in northern Egypt, 7 although the characterizations of these isolates were incomplete.Sparsomycin (1) has two stereocenters, the chiral carbon derived from an amino acid moiety and the S1sulfoxide unit. The earlier structural studies 2 had established the chiral carbon stereochemistry as

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