Apoptosis[1]
Isoalantolactone targets multiple signaling pathways. Through inhibiting NF-κB signaling, isoalantolactone exerts its anti-inflammatory effects, which are involved in the neuroprotection of isoalantolactone. It mediates the degradation of BCR-ABL protein in imatinib-resistant CML cells by down-regulating survivin. It also acts as an alkylating agent, inducing apoptosis in various cell types. Its antifungal and antimicrobial activities have also been reported.

When it comes to the K562 human leukaemia cell line, isoalantolactone shows good cytotoxic action (IC50=1.2 μM) [1]. Using PANC-1, BxPC3, and HPAC cell lines, the cytotoxic effect of isoalantolactone on pancreatic cancer is assessed. A 24-hour dose-dependent inhibition of PANC-1 cell growth is seen upon isoalantolactone treatment. At 80 µM, the inhibition rate is greater than 90%, while 40 µM is the concentration required to provide 50% growth inhibition (IC50). When BxPC3 and HPAC cells are treated with isoalantolactone, a comparable pattern of cell viability reduction is shown, with IC50 values of 43 and 48 µM, respectively. Cell viability is restored by pretreatment with 3 mM N-Acetyl Cysteine (NAC), a particular ROS scavenger, suggesting that isoalantolactone has a harmful effect on cell viability by generating ROS[2].
In vitro, isoalantolactone exhibits anti-inflammatory, antimicrobial, and antiproliferative properties. It inhibits the growth of cancer cells and induces apoptosis. Isoalantolactone has been shown to mediate the degradation of BCR-ABL protein in imatinib-resistant CML cells by down-regulating survivin. It acts as an alkylating agent and an inducer of apoptosis. It also demonstrates antimicrobial activity against various pathogens, including bacteria and fungi.

The assessment of the acute and long-term harmful effects of isoalantolactone in CD1 mice is done by comparing the body weight, blood biochemistry, and liver and kidney histology of the animals to the control groups. Mice respond effectively to isoalantolactone, and at 100 mg/kg, there are no signs of pharmacotoxicity or mortality observed in either of the two trial periods (7 & 30 days). Throughout the two study periods, food consumption and body weight increases were similar in control and treated mice, and drug-related alterations in blood biochemistry and histopathological markers were not seen. Hematoxylin and eosin staining is used to evaluate the histological alterations in the liver and kidneys, and the results are associated with indicators of renal and liver function. There are no discernible morphological alterations in the kidney and liver structures of the treatment and control groups. On dosing day 7, the treatment group's serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) slightly increase, but this increase is not substantially different (P<0.05) from the control group. At dosing day 7, there is a statistically significant rise in the total bilirubin (TBIL) concentration in the treatment group (1.43±0.26 vs. 0.76±0.12 in the control, P<0.05). On dosing day 7, there is no significant difference (P<0.05) observed in the changes in renal function biomarkers between the control and treatment groups' serum. In the therapy group, there is a little increase in creatinine (Cr) concentration and a slight decrease in blood urea nitrogen (BUN) concentration. When mice receive a 30-day injection of isoalantolactone at a dose of 100 mg/kg, the serum levels of AST, ALT, TBIL, and BUN marginally decrease[2].
In vivo, isoalantolactone has been studied for its anti-inflammatory and neuroprotective effects. Through inhibiting NF-κB signaling, isoalantolactone exerts its anti-inflammatory effects which are involved in neuroprotection. It has shown antimicrobial and antitumor effects in animal models. However, specific in vivo efficacy data in animal models are not extensively detailed in the available literature. The compound is a research tool for studying apoptosis and inflammation.

In vitro enzyme/receptor binding assays for isoalantolactone are not typical because it acts as an alkylating agent rather than a specific enzyme inhibitor. However, its ability to inhibit NF-κB activation can be assessed using electrophoretic mobility shift assays (EMSA) or luciferase reporter assays. Its alkylating activity can be assessed by measuring its reaction with nucleophilic compounds. Apoptosis induction can be measured by caspase activity assays.

Cell viability is assessed by MTT assay. Briefly PANC-1, BxPC3, and HPAC cells are treated with DMSO or Isoalantolactone (5, 10, 20, 40, 80 and 100 μM) in the presence or absence of 3 mM NAC for 24 h. Following treatment, the MTT reagent is added (500 µg/mL) and cells are further incubated at 37°C for 4 h. Subsequently 150 μL DMSO is added to dissolve farmazan crystals and absorbance is measured at 570 nm in a microplate reader. The percentage of cell viability is calculated[2].

In vivo animal experiments for isoalantolactone are conducted in rodent models of inflammation and cancer. Mice are administered isoalantolactone via oral or intraperitoneal injection, and inflammatory markers or tumor growth are assessed. However, detailed protocols are not extensively documented in the available literature.

Isoalantolactone has a molecular weight of 232.32 g/mol and a molecular formula of C15H20O2. It is an eudesmane-type sesquiterpene lactone. The compound should be stored under recommended conditions. Detailed pharmacokinetic parameters such as half-life, Cmax, and bioavailability have not been extensively reported. As a natural product, isoalantolactone may have limited oral bioavailability.

The toxicological profile of isoalantolactone has not been extensively characterized. As an alkylating agent, the compound may have potential toxicity to normal cells. No significant toxicity has been reported in the available literature at therapeutic concentrations. However, comprehensive toxicology studies would be necessary to fully assess its safety for clinical development.

[1]. Cytotoxic Michael-type amine adducts of alpha-methylene lactones alantolactone and isoalantolactone. Bioorg Med Chem Lett. 2001 Feb 12;11(3):429-31.

[2]. Isoalantolactone induces reactive oxygen species mediated apoptosis in pancreatic carcinoma PANC-1 cells. Int J Biol Sci. 2012;8(4):533-47.

Isoaranolactone is a eucalyptane lactone sesquiterpene lactone isolated from Inula helenium. It possesses apoptosis-inducing, antifungal, and plant metabolite-like properties. It is a sesquiterpene lactone and also a eucalyptane sesquiterpene compound. Isoaranolactone has been reported to exist in Inula grandis, Carpesium macrocephalum, and several other organisms with relevant data.
Isoalantolactone is an eudesmane-type sesquiterpene lactone with anti-inflammatory, antimicrobial, antitumor, and neuroprotective effects. It is also known as ISA. Isoalantolactone acts as an alkylating agent and an inducer of apoptosis. It mediates the degradation of BCR-ABL protein in imatinib-resistant CML cells by down-regulating survivin. Isoalantolactone is a research compound with potential applications in cancer and inflammatory diseases.

C15H20O2

242.32

232.146

470-17-7

73285

White to off-white solid powder

1.1±0.1 g/cm3

364.9±42.0 °C at 760 mmHg

152.7±25.3 °C

0.0±0.8 mmHg at 25°C

1.527

3.7

0

2

0

17

409

4

C[C@]12CCCC(=C)[C@@H]1C[C@H]3[C@@H](C2)OC(=O)C3=C

CVUANYCQTOGILD-QVHKTLOISA-N

InChI=1S/C15H20O2/c1-9-5-4-6-15(3)8-13-11(7-12(9)15)10(2)14(16)17-13/h11-13H,1-2,4-8H2,3H3/t11-,12+,13-,15-/m1/s1

(3aR,4aS,8aR,9aR)-8a-methyl-3,5-dimethylidene-3a,4,4a,6,7,8,9,9a-octahydrobenzo[f][1]benzofuran-2-one

NSC-601353 NSC 601353 Isoalantolactone

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~430.44 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.76 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (10.76 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (10.76 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)