Lonidamine: a non-mutagenic antitumor agent

Forster, Roy; Campana, A.; D'Onofrio, E.; Henderson, L.M.; Mosesso, Pasquale; Barcellona, P. Scorza

doi:10.1093/carcin/11.9.1509

Cited by 16 publications

(5 citation statements)

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“…The limitations of 3-BrPA are as follows: its rapid inactivation or resistance in glutathione-rich tumors, nonselective alkylation properties, potential for off-target interactions with unknown proteins, and challenges associated with penetrating the blood–brain barrier for treating gliomas [ 132 , 133 , 134 , 135 ]. LND, a selectively active compound against a wide range of tumors that is approved for use in certain countries, exhibits limited efficacy as a standalone chemotherapeutic agent for inhibiting cancer cell growth, both in vivo and in vitro [ 136 ]. However, when combined with other chemotherapeutic agents, LND demonstrates nonoverlapping toxicities [ 137 ].…”

Section: Hk II Inhibitorsmentioning

confidence: 99%

The Promoting Role of HK II in Tumor Development and the Research Progress of Its Inhibitors

Liu,

Lu,

Taledaohan

et al. 2023

Molecules

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Increased glycolysis is a key characteristic of malignant cells that contributes to their high proliferation rates and ability to develop drug resistance. The glycolysis rate-limiting enzyme hexokinase II (HK II) is overexpressed in most tumor cells and significantly affects tumor development. This paper examines the structure of HK II and the specific biological factors that influence its role in tumor development, as well as the potential of HK II inhibitors in antitumor therapy. Furthermore, we identify and discuss the inhibitors of HK II that have been reported in the literature.

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Section: Hk II Inhibitorsmentioning

confidence: 99%

The Promoting Role of HK II in Tumor Development and the Research Progress of Its Inhibitors

Liu,

Lu,

Taledaohan

et al. 2023

Molecules

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“…The low toxicity of LND (LDs, in mice and rats (mg/kg): 900,1700 orally; 435, 525 ip.) (Heywood et a1.,, 1981) and its non-mutagenic properties (Forster et al, 1990) make LND very attractive for the treatment of some kinds of tumours. At the same time an oral daily dose of LND cannot exceed 450 mg (or 0.02 mM/kg) as shown clinically (Robustelli & Pedrazzoli, 1991).…”

Section: Hyperthermia and Lonidaminementioning

confidence: 99%

INCREASING THE EFFICIENCY OF PHOTOSENSITIZED DAMAGE OF EHRLICH ASCITES CARCINOMA CELLS USING HAEMATOPORPHYRIN DERIVATIVE OR CHLORIN-e6 IN COMBINATION WITH LONIDAMINE

Chekulayev¹,

Shevchuk²,

Chekulayeva³

et al. 1996

Proceedings of the Estonian Academy of Sciences. Biology

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Lonidamine (a dichlorinated derivative of indazole-3-carboxylic acid) is an antispermatogenic and anticancer drug, which is believed to act as an inhibitor of energy metabolism. In this study the effect of lonidamine (LND) on the efficacy of photodynamic therapy of tumour was investigated. In in vitro experiments the presence of 0.25 mM LND increases synergistically (up to 2 fold) the intensity of hematoporphyrin derivative (HpD) or chlorin-eg trimethylester photosensitized damage of Ehrlich ascites carcinoma cells. Considerable inhibition of Ehrlich carcinoma rate growth in mice (the ascites form of tumour) was observed in vivo when HpD phototherapy (up to 5 mg/kg) was combined with LND (intraperitoneal injection of 0.1 mM/kg, before photoirradiation). The analysis of the interaction between LND and in vivo HpD photodynamic therapy demonstrated an additivity of response. The present effect of LND on the efficacy of phototherapy is mainly caused by the inhibitory effect of LND on the energy production system of tumour cells. Indeed, the increase of photodamage of tumour cells induced by LND was accompanied with an acceleration of the rate of decreasing their glycolytic activity and, at higher extent, oxygen consumption. We assume that the intensification of the reduction of the ATP content under photosensitization in the presence of LND was induced mainly by the inactivation of mitochondrion. Moreover, under hypoglycaemia neoplastic cells are more sensitive toward phototherapy combined with LND. We found that the mechanism ofthe potentiating effect of LND on HpD-phototherapy probably has a highly complex character. Thus, antineoplastic effect of LND and its combination with HpD-phototherapy is enhanced with increasing extracellular levels of calcium and magnesium cations. The results obtained indicate that the potentiating action of LND on phototherapy may be also explained by the injurious effect of LND on the cytoskeleton structure and cytoplasm membrane of tumour cells.

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“…Several benzo[ g ]indazole derivatives possess a high binding affinity for estrogen receptor [13], inhibition of protein kinase C‐β [14], and HIV protease inhibition [15]. Indazole derivatives are widely used for antiproliferative treatment such as lung, breast, prostate, and brain diseases [16–18]. Indazole and its derivatives furnished with different functional groups represent significant pharmacological activities and serve as structural motifs in drug molecules [19,20].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, spectral, crystal structure, drug‐likeness, in silico, and in vitro biological screening of halogen [Cl, Br] substituted N‐phenylbenzo[g]indazole derivatives as antimicrobial agents

Murugavel

Jayakumar

Chandrasekaran

et al. 2021

Journal of Heterocyclic Chem

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The N‐phenylbenzo[g]indazole derivatives, 3‐(4‐chlorophenyl)‐3,3a,4,5‐tetrahydro‐N‐phenylbenzo[g]indazole‐2‐carbothioamide (4CLPBIC), 3‐(4‐bromophenyl)‐3,3a,4,5‐tetrahydro‐N‐phenylbenzo[g]indazole‐2‐carbothioamide (4BRPBIC), and 3‐(3‐bromophenyl)‐3,3a,4,5‐tetrahydro‐N‐phenylbenzo[g]indazole‐2‐carbothioamide (3BRPBIC), were synthesized by the one‐pot green amalgamation of solvent‐free granulating methodology procedure at room temperature. The synthesized crystals were characterized by single‐crystal X‐ray diffraction (SC‐XRD), FT‐IR, FT‐Raman, NMR, and UV–Vis techniques. The molecular geometries from XRD experimental values of synthesized compounds 4CLPBIC, 4BRPBIC, and 3BRPBIC in the ground state are compared theoretically by applying the density functional theory (DFT), a method with the B3LYP/6‐311G(d,p) basis set using Gaussian 09 software. The vibrational assignments of the synthesized compounds were studied based on potential energy distribution (PED) by the VEDA4 program. The scaled DFT/B3LYP/6‐311G(d,p) results show the best agreement with the experimental values. Computational 1H and 13C NMR were acquired by utilizing gauge‐independent atomic orbital (GIAO) procedure, and chemical shift results are in good agreement with the experimental values. A web‐based theoretical investigation was performed to understand the drug‐likeness and ADMET properties of the compounds. Molecular docking studies were carried out against bacterial cholesterol inhibitor block and inhibitor of lanosterol‐14α‐demethylase CYP51 used in the treatment of topical and systemic mycoses in fungal to understand the inhibitory activity of synthesized compounds. The synthesized molecules were also tested for antibacterial and antifungal activities.

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Lonidamine: a non-mutagenic antitumor agent

Cited by 16 publications

References 0 publications

The Promoting Role of HK II in Tumor Development and the Research Progress of Its Inhibitors

The Promoting Role of HK II in Tumor Development and the Research Progress of Its Inhibitors

INCREASING THE EFFICIENCY OF PHOTOSENSITIZED DAMAGE OF EHRLICH ASCITES CARCINOMA CELLS USING HAEMATOPORPHYRIN DERIVATIVE OR CHLORIN-e6 IN COMBINATION WITH LONIDAMINE

Synthesis, spectral, crystal structure, drug‐likeness, in silico, and in vitro biological screening of halogen [Cl, Br] substituted N‐phenylbenzo[g]indazole derivatives as antimicrobial agents

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