Hybrid anticancer agents: Isothiocyanate–progesterone conjugates as chemotherapeutic agents and insights into their cytotoxicities

Adsule, Shreelekha; Banerjee, Sanjeev; Ahmed, Fakhara; Padhyé, Subhash; Sarkar, Fazlul H.

doi:10.1016/j.bmcl.2009.11.128

Cited by 32 publications

(17 citation statements)

References 39 publications

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“…Recently, it has been found that naturally occurring isothiocyanates play a significant role in the cancer chemopreventive activity of these plant species [1–2], and thus, many of such analogues containing the isothiocyanate motif have been synthesized for potential medical applications [3–6]. Morevoer, isothiocyanates are pivotal intermediates in organic synthesis, especially in the synthesis of various heterocyclic compounds [7–8] and unsymmetric thioureas [9–12].…”

Section: Introductionmentioning

confidence: 99%

A general and facile one-pot process of isothiocyanates from amines under aqueous conditions

Sun¹,

Li²,

Shao³

et al. 2012

Beilstein J. Org. Chem.

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SummaryA general and facile one-pot protocol for the preparation of a broad range of alkyl and aryl isothiocyanates has been developed from their corresponding primary amines under aqueous conditions. This synthetic process involves an in situ generation of a dithiocarbamate salt from the amine substrate by reacting with CS2 followed by elimination to form the isothiocyanate product with cyanuric acid as the desulfurylation reagent. The choice of solvent is of decisive importance for the successful formation of the dithiocarbamate salt particularly for highly electron-deficient substrates. This novel and economical method is suitable for scale-up activities.

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Section: Introductionmentioning

confidence: 99%

A general and facile one-pot process of isothiocyanates from amines under aqueous conditions

Sun¹,

Li²,

Shao³

et al. 2012

Beilstein J. Org. Chem.

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“…Moreover, there have been some indications that SFN may help in the prevention and treatment of patients with oxidative damage and suppress the specific inflammatory factors [14, 15]. Many studies indicate a positive correlation between the consumption of cruciferous vegetables and the decreased incidence of some tumors including prostate [16], cervical [17], ovarian [18], lung [19], and gastrointestinal tract [20, 21]. In addition to the actions of inhibiting cell proliferation and increasing apoptosis [22], other mechanisms have also been proposed to rationalize the anticarcinogenic effect of SFN, such as the anti-inflammatory and antioxidant activities, the induction of phase-II detoxification enzymes, the inhibition of cyclooxygenase 2 (COX-2) [23], the effect on NF κ B transcription factors [24], the inhibition of matrix metalloproteinase (MMP), the effect on protein kinases, and others [25, 26].…”

Section: Introductionmentioning

confidence: 99%

Apoptosis Induction in Primary Human Colorectal Cancer Cell Lines and Retarded Tumor Growth in SCID Mice by Sulforaphane

Chen

Tang

Hsu

et al. 2012

Evidence-Based Complementary and Alternative Medicine

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We have investigated the anticancer effects of the dietary isothiocyanate sulforaphane (SFN) on colorectal cancer (CRC), using primary cancer cells lines isolated from five Taiwanese colorectal cancer patients as the model for colorectal cancer. SFN-treated cells accumulated in metaphase (SFN 6.25 μM) and subG1 (SFN 12.5 and 25 μM) as determined by flow cytometry. In addition, treated cells showed nuclear apoptotic morphology that coincided with an activation of caspase-3, and loss of mitochondrial membrane potential (ΔΨm). Incubations at higher SFN doses (12.5 and 25 μM) resulted in cleavage of procaspase-3 and elevated caspase-2, -3, -8, and -9 activity, suggesting that the induction of apoptosis and the sulforaphane-induced mitosis delay at the lower dose are independently regulated. Daily SFN s.c. injections (400 micromol/kg/d for 3 weeks) in severe combined immunodeficient mice with primary human CRC (CP1 to CP5) s.c. tumors resulted in a decrease of mean tumor weight by 70% compared with vehicle-treated controls. Our findings suggest that, in addition to the known effects on cancer prevention, sulforaphane may have antitumor activity in established colorectal cancer.

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“…The antitumor activities of various ITCs have been reported recently including growth inhibiting properties in human ovarian [11,19,31,32] and breast [33,34] cancers, where also their anti-angiogenic and anti-metastatic effects have been described [35,36].…”

Section: Discussionmentioning

confidence: 99%

Synthetic isothiocyanate indole-3-ethyl isothiocyanate (homoITC) enhances sensitivity of human ovarian carcinoma cell lines A2780 and A2780/CP to cisplatin

Stehlik

Paulíková²,

Hunáková³

2010

neo

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Isothiocyanates (ITCs), popular chemopreventive agents present in cruciferous vegetables, prove growth-inhibiting and apoptosis-inducing activities in cancer cell lines in vitro. Our study presents a new synthetic ITC derivate indol-3-ethyl isothiocyanate (homoITC) as an effective modulator of cellular proliferation and inducer of apoptosis with potential utility as an anticancer drug or a sensitizer to routinely used chemotherapeutic agent cisplatin (cis-Pt).We analyzed the growth inhibitory effects of homoITC in the human ovarian carcinoma cell line A2780 and its cisplatinresistant variant A2780/CP using MTT-test and its apoptosis-inducing properties by flow cytometry and caspase 3 activation. Combination index (CI) values from Calcusyn software were used to characterize the interactions of homoITC and cis-Pt as synergistic (CI<1), additive (CI=1), or antagonistic (CI>1). Significant synergistic effect in growth inhibition of homoITC (5 -15 µM) and cis-Pt (2.5 -10 µM) on A2780 parental cell line (CI from 0.42 to 0.85) was also observed on A2780/CP resistant subline (CI from 0.18 to 0.73) for 10-50 µM cis-Pt concentrations and the same concentrations of homoITC. Synergy in growth inhibition correlated with the potential of homoITC to stimulate apoptosis induced by cis-Pt.We conclude that homoITC may be worth of further studies assessing its value in the ovarian cancer treatment and elucidating mechanisms of its action.

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Hybrid anticancer agents: Isothiocyanate–progesterone conjugates as chemotherapeutic agents and insights into their cytotoxicities

Cited by 32 publications

References 39 publications

A general and facile one-pot process of isothiocyanates from amines under aqueous conditions

A general and facile one-pot process of isothiocyanates from amines under aqueous conditions

Apoptosis Induction in Primary Human Colorectal Cancer Cell Lines and Retarded Tumor Growth in SCID Mice by Sulforaphane

Synthetic isothiocyanate indole-3-ethyl isothiocyanate (homoITC) enhances sensitivity of human ovarian carcinoma cell lines A2780 and A2780/CP to cisplatin

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