Mechanism of Action of Alpha-Methylene-Gamma-Lactone Derivatives of Substituted Nucleic Acid Bases in Tumour Cells

Panda, Chinmay Kumar; Choudhury, Kanakendu; Sanyal, Utpal; Chakraborti, S. K.

doi:10.1159/000238667

Cited by 2 publications

(1 citation statement)

References 8 publications

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“…A number of germacranolide-type sesquiterpene lactones with an α-methylene-γlactone derivatives obtained from natural sources have been demonstrated to exhibit pharmaceutically interesting biological activities in animals and plants. DHCL and costunolide have been demonstrated to show antitumor activity, anti-inflammatory activity, and the induction of apoptosis [26][27][28][29][30][31][32]. These compounds are also demonstrated to act as germination stimulants for the root parasitic broomrapes Orobanche cumana Wallr.…”

Section: Introductionmentioning

confidence: 99%

Dehydrocostus lactone, a naturally occurring polar auxin transport inhibitor, inhibits epicotyl growth by interacting with auxin in etiolated Pisum sativum seedlings

et al. 2019

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We have isolated germacranolide-type sesquiterpene lactones with an α-methylene-γ-lactone moiety, dehydrocostus lactone (DHCL), costunolide, santamarine, and a novel compound denoted artabolide [3-hydroxy-4,6,7(H)-germacra-1(10),11(13)-dien-6,12-olide] from oriental medicinal Asteraceae plants as novel naturally occurring inhibitors of polar auxin transport detected by the radish hypocotyl bioassay. To investigate the mode of action of natural sesquiterpene lactones on the inhibition of polar auxin transport as well as its relation to the growth of seedlings, the function of DHCL on growth and auxin dynamics in etiolated pea seedlings was studied intensively. DHCL reduced polar auxin transport in a dose-dependent manner together with the inhibition of the accumulation of mRNA of PsAUX1 and PsPIN1 genes encoding influx and efflux carrier proteins of auxin, respectively. DHCL applied to the apical hook region as a lanolin paste substantially inhibited elongation growth in the subapical region of epicotyls in intact etiolated pea seedlings, coupled with a significant reduction of endogenous levels of indole-3-acetic acid (IAA). DHCL also revealed the inhibition of IAA-induced cell elongation in etiolated pea epicotyl segments by affecting IAA-induced changes in the mechanical properties of cell walls. These facts suggest that germacranolide-type sesquiterpene lactones with an α-methylene-γ-lactone moiety affect the expression of PsAUX1 and PsPINs genes, and then inhibit polar auxin transport and reduce endogenous levels of IAA necessary for stem growth in etiolated pea seedlings. These compounds are also suggested to show the inhibitory effects on auxin action in pea stem growth.

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Section: Introductionmentioning

confidence: 99%

Dehydrocostus lactone, a naturally occurring polar auxin transport inhibitor, inhibits epicotyl growth by interacting with auxin in etiolated Pisum sativum seedlings

et al. 2019

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Evaluation of ‘cypenhymustine’, a new anticancer compound, in murine tumour models

Sanyal¹,

Bhattacharya²,

Sadhu³

et al. 1993

Cancer Letters

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'Cypenhymustine', 3-[2-[bis(2'-chloroethyl)-amino] ethyl]-5,5- tetramethylenehydantoin, has been synthesised as a potential analog of spiromustine (NSC 172112). The LD50 value was determined in Swiss male mice and found to be 65.0 mg/kg by single i.p. injection. In in vivo screening experiments, three parameters, namely, ascites cell count, ascites fluid measurement and increase in life span (ILS) of drug-treated over control Swiss mice were studied in three murine ascites tumours namely Ehrlich ascites carcinoma (EAC), sarcoma-180 (S-180) and Dalton's lymphoma (DL). Cypenhymustine exhibited a very high percentage of inhibition of both the ascites cell and fluid in these models and also displayed excellent reproducible ILS activity (ILS values of 151 in EAC, 157 in S-180 and 181 in DL at the optimum dose of 3 mg/kg for days 1-7 treatment following tumour transplant on day 0) having a 'curative' effect (1-2 animals: 6 having > 60 days survival rate). The chemical alkylating activity has been compared with spiromustine and another antitumour agent namely nor-HN2.

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Mechanism of Action of Alpha-Methylene-Gamma-Lactone Derivatives of Substituted Nucleic Acid Bases in Tumour Cells

Cited by 2 publications

References 8 publications

Dehydrocostus lactone, a naturally occurring polar auxin transport inhibitor, inhibits epicotyl growth by interacting with auxin in etiolated Pisum sativum seedlings

Dehydrocostus lactone, a naturally occurring polar auxin transport inhibitor, inhibits epicotyl growth by interacting with auxin in etiolated Pisum sativum seedlings

Evaluation of ‘cypenhymustine’, a new anticancer compound, in murine tumour models

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