CN113754649B - Indole derivative containing oxadiazole, triazole and pyrazole structural units and application thereof - Google Patents
Indole derivative containing oxadiazole, triazole and pyrazole structural units and application thereof Download PDFInfo
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Abstract
The invention relates to an indole derivative structure containing diazole, triazole and pyrazole structural units and application thereof. The compound has a structure shown as a general formula (I):
wherein X = O, S, N-NH 2 . The indole is used as a mother nucleus, pyrazole is introduced into the 3-position, and a series of indole derivatives containing oxadiazole, triazole and pyrazole structures are synthesized, and the compounds have good cytotoxicity on human hepatoma cells HepG2, human non-small cell lung cancer cells A549, human prostate cancer cells PC-3 and human chronic myelogenous leukemia cells K562.
Description
Technical Field
The invention relates to the technical field of medicinal chemistry, in particular to an indole derivative structure containing oxadiazole, triazole and pyrazole structural units and application thereof.
Background
The incidence of malignant tumors has increased year by year due to the influence of many factors such as environment, and cancer has become the second leading killer of human health. The serious threat of cancer to human health has not been effectively controlled. Therefore, research and development of novel anticancer drugs with low toxicity and high efficiency are of great importance.
Indole structure is commonly present in natural and synthetic drugs, and has biological activities of anti-tumor, anti-oxidation, antibiosis and the like. Different substituents are introduced to the 3-position of indole, and modification and reconstruction of the structure are always hot spots of drug research. The marketed antitumor drugs such as the lucaparib (Rucaparib), the oxitinib mesylate (Osimetinib), the Panobinostat (Panobinostat), the Melatonin (Melatonin) and the like all take indole as a framework, so that the treatment effect is good, the side effect after healing is small, and the application prospect is very wide.
In addition, the pyrazole and the derivatives thereof also have better biological activity, such as spasm resistance, inflammation resistance, bacteria resistance, tumor resistance, depression resistance and the like, and are widely used in the field of medicines. In order to search for an efficient and low-toxicity antitumor compound, the invention takes 3-pyrazole indole as a framework and sulfydryl as a connecting chain, introduces an oxadiazole or triazole structure which can improve the biological activity of a target compound into the system, synthesizes the 3-pyrazole indole compound containing an oxadiazole or triazole structural unit, inspects the antitumor activity of the compound, and provides a certain reference value for the research, development and creation of novel antitumor drugs.
Organisms of indole derivatives the activity study progressed as follows:
zhang et al [ Zhang, D t.; wang, G t.; zhao, G l.; xu, W r.; synthesis and cytoxic activity of novel 3- (1H-indol-3-yl) -1H-pyrazole-5-carbohydrazide derivatives [ J].Eur.J.Med.Chem.,2011,46(12):5868-5877.]A series of 3-pyrazole indole derivatives are designed and synthesized, and the anti-proliferation activity of all compounds on 4 human tumor cell strains is detected by adopting an MTT method. The results show that the cytotoxicity of most compounds to HepG-2 (human lung cancer cells), BGC823 (human gastric cancer cells) and BT474 (human breast cancer cells) is higher than that of a positive control drug 5-fluorouracil. The highest inhibition effect of the compound on BT474 cells can reach 52 times that of a control drug, and the IC is 50 (half maximal inhibitory concentration) was 1.39. Mu. Mol/L.
Kamath et al [ Kamath, pr.; joseph, M; ajees, a.; bisindole-oxadiazole hybrids, T3P ((R)) -mediated synthesis,and appraisal of their apoptotic,antimetastatic,and computational Bcl-2 binding potential[J].J.Biochem.Mol.Toxic.,2017,31(11):e21962.]A green and efficient method is developed to synthesize a series of novel bis-indole derivatives containing oxadiazole. Certain compounds have selective toxicity, IC, on MCF-7 cells 50 The minimum is 8.45 mu mol/L, and the anti-proliferative effect is stronger than that of vincristine. Further mechanism research shows that the compounds can also trigger G1 phase cell cycle block of MCF-7 cells; and inducing the programmed cell death by activating caspase-2, caspase-9 (cysteine protein) and inhibiting the activity of anti-apoptotic protein Bcl-2.
Bhale et al [ Bhale, p.s.; bandgar, bp.; dongare, S b.; shringaree, s.n.; sirsat, D m.; chavan, H V. Keten dithioacetic medium synthesized of 1,3,4,5-tetrastiglated pyridine derivatives and the biological evaluation [ J].Phosphorus,sulfur,and silicon and the related elements,2019,194(8):843-849.]A series of novel indole derivatives containing pyrazole heterocycles were reported and all compounds were tested for cytotoxicity against MCF-7 (human breast cancer cells) using the SRB method. Among them, compound 4 exhibited the strongest antiproliferative activity against MCF-7, GI 50 The value (the concentration of the drug which inhibits cell growth by 50%) was 15.6. Mu. Mol/L, and the toxicity to normal monkey kidney cells was extremely low. The structure-activity relationship shows that the introduction of electron-withdrawing groups on the benzene ring can improve the antitumor activity of the compound on breast cancer. In addition, most compounds also exhibit good anti-inflammatory and antioxidant activity (DPPH, NO, H2O2, SOR).
Naaz et al [ Naaz, f., 2020; ahmad, f.; lane, b.a.; pokharel, Y r.; fuloria, N K; fuloria, S; ravichandran, m.; pattabhiraman, l.; shafi, s.; yar, M S.design and synthesis of new 1,3,4-oxadizole and 1,2,4-triazine based topsin analogs as anti-promoting agent targeting tubulin].Bioorg.Chem.,2020,95:103519.]And a series of Topsentin alkaloid analogues are designed and synthesized by replacing imidazole rings in Topsentin with 1,2,4-triazole and 1,3,4-thiadiazole groups. The compound has good effect on melanoma, colon cancer cells and breast cancer cell linesAnti-proliferation Activity (IC) 50 The lowest values were 2.42, 3.06, 3.30. Mu. Mol/L, respectively), and exhibited a higher level of doxorubicin (IC) than the control drug on MCF-7 cells 50 =6.31 μmol/L) stronger effect.
Disclosure of Invention
The invention provides an indole compound containing diazole, triazole and pyrazole structural units, or a stereoisomer thereof, or a salt or solvate thereof.
It is still another object of the present invention to provide a composition comprising the above compound or a stereoisomer thereof, or a salt or solvate thereof.
It is a further object of the present invention to provide the above compounds or stereoisomers thereof, or salts or solvates thereof, or the use of said compositions.
The invention also provides a method for applying the compound or the stereoisomer thereof, the salt thereof or the solvate thereof or the composition to the tumor resistance.
In order to realize the purpose, the invention adopts the following technical scheme:
an indole compound of oxadiazole, triazole and pyrazole structural units or a stereoisomer thereof, or a salt or solvate thereof, wherein the compound has a structure shown as a general formula (I):
wherein X = O, S or N-NH 2
R is selected from any substituted or unsubstituted aryl and any substituted or unsubstituted heterocycle.
Further preferably, R is selected from substituted or unsubstituted aryl, substituted or unsubstituted heterocycle;
preferably, R is selected from substituted or unsubstituted C 6 -C 15 Aryl, substituted or unsubstituted C 6 -C 10 One or more of the hetero rings, wherein said substitution means by C 1 -C 6 One or one of alkoxy, amino, hydroxy, halogenMore than one substitution;
more preferably, R is selected from substituted or unsubstituted phenyl, substituted or unsubstituted pyridine and, substituted or unsubstituted pyrrolyl, substituted or unsubstituted indolyl. Wherein said substitution is by C 1 -C 6 One or more of alkoxy, amino, hydroxyl and halogen;
most preferably, R is selected from phenyl, 2-fluorophenyl, 2-chlorophenyl, 2-bromophenyl, 2-hydroxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-aminophenyl, 4-methoxyphenyl, 3,5-dichlorophenyl, 3,4,5-trimethoxyphenyl, pyridyl, indolyl, pyrrolyl. The indole compound containing the structural units of the diazole, the triazole and the pyrazole or a stereoisomer thereof, or a salt or a solvate thereof is selected from the following compounds:
the invention also provides an intermediate compound for preparing the indole compound containing the structural units of the diazole or triazole and the pyrazole, or a stereoisomer thereof, or a salt or a solvate thereof, which is shown as follows:
the invention also provides a preparation method of the indole compound containing the diazole or triazole and pyrazole structural unit or a stereoisomer thereof, or a salt or solvate thereof, which comprises the following steps:
the invention also provides a composition which contains the compound or the stereoisomer thereof, or the salt thereof or the solvate thereof, and an auxiliary agent or an anti-tumor medicinal preparation which can be used for treating tumors; preferably, the dosage form of the composition is selected from pills, granules, tablets, oral liquid, injection, powder and the like.
The compound or the stereoisomer thereof, the salt thereof or the solvate thereof, or the composition can be used for treating tumors, preferably the tumors are lung cancer, liver cancer, prostatic cancer, colon cancer, cervical cancer or leukemia; more preferably, the tumor is lung cancer, liver cancer, prostate cancer and leukemia.
The invention also provides a method for preparing the anti-tumor medicine. Allowing said compound or stereoisomer thereof, or salt or solvate thereof, or said composition to act on tumor cells or their living environment; preferably, the tumor cells are liver cancer cells, lung cancer cells, prostate cancer cells and leukemia cells.
The invention also provides a method for preparing an antitumor medicament, which comprises the step of contacting plants with the compound or the stereoisomer thereof, the salt thereof or the solvate thereof, or the composition.
The term "substituted" as used herein means that any one or more hydrogen atoms on the designated atom or group is replaced with the designated group of choice, provided that the general valence of the designated atom is not exceeded. If not otherwise stated, substituents are named to the central structure. For example, it is understood that when (cycloalkyl) alkyl is a possible substituent, the point of attachment of the substituent to the central structure is in the alkyl moiety. As used herein, a cyclic double bond is a double bond formed between two adjacent ring atoms (e.g., C = C, C = N or N = N). When referring to substitution, especially polysubstitution, it is meant that the multiple substituents are substituted at various positions on the indicated group, e.g., dichlorophenyl means 1,2-dichlorophenyl, 1,3-dichlorophenyl, and 1,4-dichlorophenyl.
Combinations of substituents and or variables are permissible only if such combinations result in stable compounds or useful synthetic intermediates. A stable compound or stable structure implies that the compound is sufficiently stable to be isolated in useful purity from the reaction mixture and subsequently formulated to form an effective therapeutic agent. Preferably, the compounds described so far do not contain N-halogen, S (O) 2 H or an S (O) H group.
The term "aryl" refers to a monocyclic or bicyclic aromatic hydrocarbon group having 6 to 12 carbon atoms in the ring portion, such as phenyl, each of which may be substituted.
The term "halogen" or "halogen atom" refers to chlorine, bromine, fluorine and iodine.
The term "heteroaryl" refers to substituted and unsubstituted aromatic 5 or 6 membered monocyclic groups, 9-or 10-membered bicyclic groups, and 11 to 14 membered tricyclic groups having at least one heteroatom (O, S or N) in at least one ring, preferably 1,2 or 3 heteroatoms selected from O, S and N. The heteroatom-containing heteroaryl groups can contain one or two oxygen or sulfur atoms per ring and/or from 1 to 4 nitrogen atoms, provided that the total number of heteroatoms in each ring is 4 or less and there is at least one carbon atom in each ring. The fused rings making up the bicyclic and tricyclic groups may contain only carbon atoms and may be saturated, partially saturated, or unsaturated. The nitrogen and sulfur atoms may be oxidized and the nitrogen atoms may be quaternized. Bicyclic or tricyclic heteroaryl groups must include at least one fully aromatic ring, and the other fused rings may be aromatic or non-aromatic. The heteroaryl group may be linked to any available nitrogen or carbon atom of any ring. If the other ring is cycloalkyl or heterocyclic, it is additionally optionally substituted with = O (oxygen), as valency permits.
Exemplary monocyclic heteroaryl groups include pyrrolyl, pyridinyl and the like.
The compounds of the invention are understood to include both the free form and salts thereof, unless otherwise indicated. The term "salt" means an acid and/or base salt formed from an inorganic and/or organic acid and a base. In addition, the term "salt" may include zwitterions (inner salts), such as when the compound of formula I contains a basic moiety, such as an amine or pyridine or imidazole ring, and an acidic moiety, such as a carboxylic acid. Pharmaceutically acceptable (i.e., non-toxic, physiologically acceptable) salts are preferred, such as acceptable metal and amine salts, wherein the cation does not contribute significantly to the toxicity or biological activity of the salt. However, other salts may be useful, such as separation or purification steps in the preparation process, and are therefore included within the scope of the present invention.
When substituents are mentioned, such as halogen, aryl, heteroaryl, hydroxy, alkoxy, amino, or when these substituents are specifically halogen, aryl, heteroaryl, alkoxy, hydroxy, amino, one to three of the above substituents are meant. Such as methylphenyl refers to phenyl substituted with one to three methyl groups.
By adopting the technical scheme, the invention synthesizes a series of indole compounds containing diazole or triazole structural units on the basis of a 3-pyrazoldole structure, and finds that the compounds have good inhibition effect on certain tumor cells and are directed at anti-tumor cells [ such as A549 (human non-small cell lung cancer cells), hep-G2 (human liver cancer cells), PC-3 (human prostate cancer cells) and K562 (human chronic myelogenous leukemia cells)]All have particularly good inhibitory effect, IC 50 The minimum can reach 10nM, which provides important scientific basis for research and development of novel high-activity antitumor drugs.
Examples
The invention is further illustrated by the following examples. It should be understood that the method described in the examples is only for illustrating the present invention and not for limiting the present invention, and that simple modifications of the preparation method of the present invention based on the concept of the present invention are within the scope of the present invention. All the starting materials and solvents used in the examples are commercially available products.
Example 1: preparation of 3- (1H-indol-3-yl) -3-oxo-propionitrile
Indole (10.00g, 85.36mmol), cyanoacetic acid (10.17g, 119.50mmol), and 100mL of acetic anhydride were put in this order in a 250mL round-bottomed flask, and refluxed at 40 ℃ for 4 hours. After the reaction is finished, standing and cooling to room temperature, carrying out suction filtration, washing for 2-3 times by using methanol, and drying to obtain a white solid with the yield of 77.3%.
Example 2: preparation of 3- (1H-indol-3-yl) -1H-pyrazol-5-amine
To a 500mL round-bottomed flask were added 3- (1H-indol-3-yl) -3-oxo-propionitrile (5.00g, 27.14mmol) and 80% hydrazine hydrate (6.79g, 169.38mmol) in this order, and about 250mL of anhydrous ethanol was added as a solvent, and the reaction system was refluxed at 80 ℃ with stirring and monitored by TLC. After the reaction is finished, standing, naturally cooling, concentrating the reaction mixture under reduced pressure to be thick, cooling, performing suction filtration, and washing with ethyl acetate for 2-3 times to obtain a brown solid with the yield of 54.1%.
Example 3: preparation of N- (3- (1H-indol-3-yl) -1H-pyrazol-5-yl) -2-chloroacetamide
A50 mL round-bottom flask was charged with 3 (2.00g, 10.09mmol) and anhydrous sodium carbonate (1.07g, 10.69mmol), followed by addition of a portion of 1,4-dioxane, followed by stirring at room temperature. Chloroacetyl chloride (1.14g, 10.09mmol) was then added to 2mL of 1, 4-dioxane (20 mL total), added dropwise to the round bottom flask and stirred for 1h. After TLC monitoring reaction, another beaker is added with 100mL of water, naCl is added, crushed ice is poured in, the reaction mixture is poured in, and the mixture is stirred until precipitation occurs, is kept stand, is filtered under reduced pressure and is washed by water, so that a gray-green solid is obtained. Drying and recrystallizing with ethanol to obtain 4. White solid, 18% yield.
Example 4: preparation of 3,5-dichlorophenylhydrazide
In a 25ml round bottom flask was added 3g ethyl 3, 5-dichlorobenzoate (1 mmol. Times.1.5 ml hydrazine hydrate), about 21ml hydrazine hydrate, reflux at 80 ℃ for 5h, placed under the refrigerator overnight, filtered to give a white solid in 81% yield.
Example 5: preparation of 4-amino-5- (3,5-dichlorophenyl) -4H-1,2,4-triazole-3-thiol
3,5-dichlorobenzoyl hydrazine (13.69 mmol), potassium hydroxide (12.68 mmol) was put in 100ml round bottom flask, 32ml ethanol was added and stirred at room temperature, and CS was gradually added dropwise 2 (12.68 mmol), stirring for 5h, filtering, washing with ethanol for several times, drying to obtain a yellow-white solid (1 mmol × 3ml hydrazine hydrate), refluxing at 80 deg.C for 5h, pouring the reaction mixture into ice water, adjusting pH to 2-3 with hydrochloric acid, standing, filtering, washing with water, and drying to obtain a white solid with a yield of 20%.
Example 6: n- (3- (1H-indol-3-yl) -1H-pyrazol-5-yl) -2- ((4-amino-5- (3,5-dichlorophenyl) -4H-1,2,4-triazol-3-yl) thio) acetamide
4-amino-5- (3,5-dichlorophenyl) -4H-1,2,4-triazole-3-thiol (1.49 mmol) and KOH (2.99 mmol) were added in sequence to a 25ml round bottom flask, 10ml of absolute ethanol was added, and after stirring at room temperature for 10min, N- (3- (1H-indol-3-yl) -1H-pyrazol-5-yl) -2-chloroacetamide (1.49 mmol) was added, and the reaction was continued for 1H. After the reaction is finished, 60ml of ice water is sequentially added into another beaker, the reaction mixture is poured while stirring, standing and suction filtration are carried out, and the ethanol is recrystallized to obtain a white solid with the yield of 45.6%.
Other objective compounds were synthesized by following the steps of example 4 and 5 using the corresponding starting materials or substituents.
The structure and nuclear magnetic resonance hydrogen spectrum and nuclear magnetic resonance carbon spectrum related characterization data of the synthesized indole compound containing the oxadiazole, triazole and pyrazole structural units are shown in table 1, and the physicochemical properties are shown in table 2.
TABLE 1 NMR hydrogen and carbon spectra data for some of the compounds
Table 2 physicochemical properties of the target compounds
Pharmacological example 1:
half inhibitory concentration IC of compound on A549 (human non-small cell lung cancer cell), PC-3 (human prostate cancer cell), hepG2 (human hepatoma cell), K562 (human chronic myeloid leukemia cell) and NRK-52E (rat tubular duct epithelial cell) measured by MTT method 50 The value is obtained.
Determination of the in vitro antitumor Activity of Compounds (Primary Screen)
Cell inoculation step (for adherent cells, suspension cells)
1. Selecting cells: selecting cells in logarithmic growth phase according to a cell growth curve;
2. digesting the cells: digesting the monolayer cultured cells with 0.25% trypsin, preparing a single cell suspension with 10% FBS-containing DMEM/1640 culture solution;
3. cell counting: firstly, soaking a cell counting plate and a blood cover plate in absolute ethyl alcohol; taking 10 mu L of cell suspension, and dripping the cell suspension on the edge of the blood cover plate to ensure that the suspension is filled between the blood cover plate and the counting plate and the blood cover plate can not overflow or overflow into the glass grooves at two sides; the number of cells in the square grid of the counting plate was observed under a microscope with l0 × objective lens. The wire pressing cells are only counted at the left side and the upper side, and the right side and the lower side are not counted; calculating according to the formula: (the sum of the number of 4 large cells/4) × 104 × cell sap volume =3 × 104 × total required cell mixture (the density is generally 3 × 104, and other densities may be used depending on the cell properties);
4. color and value (for adherent cells)
Adding 20. Mu.L of MTT solution (5 mg/mL,10% MTT), incubating for 4h, and terminating the culture; sucking out the solution in the culture plate by adopting a liquid suction mode; adding 150 mu L of DMSO into each hole to dissolve formazan particles, shaking the mixture for 10min (150 rpm/min) by using a shaking table, uniformly mixing, measuring OD values at 490 and 570nm by using a microplate reader, and recording the result. The results were analyzed using software.
Inhibition =1- (dosing OD value-blank OD value)/(negative OD value-blank OD value) × 100%;
blank control wells: 200 μ L of culture broth +150 μ L of DMSO;
negative control wells: 180 μ L cell suspension +20 μ L DMSO +20 μ LMTT +150 μ L DMSO;
adding a medicine hole: 180 μ L of cell suspension +20 μ L +20 μ LMTT +150 μ L DMSO at different concentrations of drug;
and (3) selecting a compound with the inhibition rate close to 50% to perform re-screening, preparing the compound to be tested into solutions of 10 mu M, 5 mu M, 2.5 mu M, 1.25 mu M and 0.625 mu M respectively, and adding 20 mu L of the solution into each hole to prepare 5 re-holes. The rest of the treatment steps are the primary screening of the compound. The examples of the present invention are given to illustrate the technical means of the present invention, but the contents of the examples are not limited thereto, and the experimental results of the target compounds are shown in table 3.
TABLE 3 inhibitory Activity of the target Compounds on four tumor cells
All the compounds are evaluated by MTT method on human non-small cell lung cancer cell A549, human prostate cancer cell PC-3, human liver cancer cell HepG2 and chronic myelogenous leukemia cell K562Toxicity, and the cytotoxicity of the compound on rat renal cells NRK-52E was tested to evaluate safety and selectivity. The results indicate that this class of compounds is generally more sensitive to K562 cells. Most compounds show better tumor inhibition activity than positive control drug 5-fluorouracil on A549 cells, PC-3 cells, K562 cells and HepG2 cells, the inhibition rate can reach 99.57 percent at most, and IC (integrated Circuit) is 50 The lowest value was 10nM. The IC50 value of part of the compounds can reach nanomolar scale, wherein the IC50 of the compounds 11a, 11c, 12a, 12b and 12e to A549 cells is 0.47 +/-0.07, 0.31 +/-0.06, 0.43 +/-0.10, 0.12 +/-0.05 and 0.83 +/-0.09 mu M respectively; IC of Compounds 12a, 12b, 12e on PC-3 cells 50 0.14 +/-0.01, 0.85 +/-0.72 and 0.85 +/-0.43 mu M respectively; IC of Compounds 11a, 11c, 12b, 12d, 12e on HepG2 cells 50 0.57 +/-0.15, 0.63 +/-0.25, 0.21 +/-0.07, 0.73 +/-0.15 and 0.80 +/-0.09 mu M respectively; compounds 11a, 11b, 11c, 12a, 12b, 12c, 12e, 12f, 13h, 13l showed better activity on K562 cells, IC 50 0.22 +/-0.06, 0.28 +/-0.01, 0.14 +/-0.06, 0.05 +/-0.02, 0.01 +/-0.01, 0.18 +/-0.02, 0.19 +/-0.09, 0.99 +/-0.52, 0.06 +/-0.02 and 0.36 +/-0.10 mu M respectively. IC of Compounds 12b, 12e against these four human tumor cells 50 All values are in the nanomolar range.
Claims (8)
1. An indole compound or a salt thereof containing an oxadiazole or triazole and a pyrazole structural unit, characterized in that: has a structure shown as general formula (I):
wherein, the first and the second end of the pipe are connected with each other,
x is O, S or NNH 2 (ii) a R is selected from substituted or unsubstituted phenyl, substituted or unsubstituted pyridyl, substituted or unsubstituted indolyl and substituted or unsubstituted pyrrolyl, wherein substituted means substituted by C 1 -C 6 One or more of alkoxy, amino, hydroxyl and halogen.
2. Indole compound or a salt thereof according to claim 1 containing oxadiazole, triazole and pyrazole building blocks, characterized in that: r is selected from phenyl, 2-fluorophenyl, 2-chlorophenyl, 2-bromophenyl, 2-hydroxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methoxyphenyl, 3,5-dichlorophenyl, 3,4,5-methoxyphenyl, pyridyl, indolyl or pyrrolyl.
3. An intermediate compound for preparing indole derivatives or salts thereof containing oxadiazole, triazole and pyrazole heterocyclic structures according to any one of claims 1-2, wherein the intermediate compound comprises: the intermediate compound has the following structural formula:
4. a method for preparing indole derivatives or salts thereof containing diazole, triazole and pyrazole structures according to any one of claims 1-2, comprising the steps of:
5. a composition comprising a compound according to any one of claims 1 to 2 or a salt thereof, and a pharmaceutically acceptable adjuvant or an antitumor agent.
6. Use of a compound or salt thereof as claimed in any one of claims 1-2, or a composition as claimed in claim 5, in the manufacture of an anti-neoplastic medicament.
7. Use according to claim 6, characterized in that: the tumor is a human tumor cell.
8. Use according to claim 7, characterized in that: the human tumor cells comprise A549 human non-small cell lung cancer cells, hepG2 human liver cancer cells, PC-3 human prostate cancer cells and K562 human chronic myelogenous leukemia cells.
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| CN111285860B (en) * | 2020-03-25 | 2021-08-10 | 贵州大学 | Indole derivatives containing disulfanyl heterocyclic structure or stereoisomer thereof, or salt or solvate thereof |
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