Role and Recent Advancements of Ionic Liquids in Drug Delivery Systems.

Advancements in the fields of ionic liquids (ILs) broaden its applications not only in traditional use but also in different pharmaceutical and biomedical fields. Ionic liquids "Solutions for Your Success" have received a lot of interest from scientists due to a myriad of applications in the pharmaceutical industry for drug delivery systems as well as targeting different diseases. Solubility is a critical physicochemical property that determines the drug's fate at the target site. Many promising drug candidates fail in various phases of drug research due to poor solubility. In this context, ionic liquids are regarded as effective drug delivery systems for poorly soluble medicines. ILs are also able to combine different anions/cations with other cations/anions to produce salts that satisfy the concept behind the ILs. The important characteristics of ionic liquids are the modularity of their physicochemical properties depending on the application. The review highlights the recent advancement and further applications of ionic liquids to deliver drugs in the pharmaceutical and biomedical fields.

(E)-2,4-Dichloro-6-{1-[(2-chloro-eth-yl)imino]-eth-yl}phenol.

The title Schiff base compound, C(10)H(10)Cl(3)NO, was prepared by the condensation of 1-(3,5-dichloro-2-hy-droxy-phen-yl)ethanone with chloro-ethyl-amine. The imine adopts an E configuration with respect to the C=N bond. The H atom of the phenolic OH group is disordered over two positions with site occupation factors of 0.52 (7) and 0.48 (7), respectively, and the major occupancy component is involved in an intramolecular N-H⋯O hydrogen bond. The compound therefore exists in an iminium-phenolate as well as in the imino-phenol form. In the crystal, mol-ecules are connected by C-H⋯O and C-H⋯Cl hydrogen bonds and Cl⋯Cl inter-actions [3.7864 (9) Å] into a three-dimensional network. In addition, inter-molecular π-π stacking inter-actions [centroid-centroid distance = 4.4312 (9) Å] are observed.

Synthesis of novel substituted pyrazole-5-carbohydrazide hydrazone derivatives and discovery of a potent apoptosis inducer in A549 lung cancer cells.

A series of novel 3-aryl-1-(4-tert-butylbenzyl)-1H-pyrazole-5-carbohydrazide hydrazone derivatives were synthesized and the effects of all the compounds on A549 cell growth were investigated. The results showed that all compounds had inhibitory effects on the growth of A549 lung cancer cells and compound (E)-1-(4-tert-butylbenzyl)-N'-(1-(5-chloro-2-hydroxyphenyl) ethylidene)-3-(4-chlorophenyl)-1H-pyrazole-5-carbohydrazide (3e) possessed the highest growth inhibitory effect and induced apoptosis of A549 lung cancer cells.

7-Chloro-4-phenethyl-2H-1,4-benzoxazin-3(4H)-one.

In the crystal structure of title compound, C(16)H(14)ClNO(2), the dihedral angle between the aromatic rings is 4.2 (2)°.

8-Chloro-4-cyclo-hexyl-2H-1,4-benzoxazin-3(4H)-one.

In the crystal structure of title compound, C(14)H(16)ClNO(2), the cyclo-hexyl ring is in a chair conformation. The molecules are connected into centrosymmetric dimers via weak C-H⋯O hydrogen bonds.

1-[(6-Chloro-3-pyrid-yl)meth-yl]-N-(4-ethoxy-phen-yl)-3-phenyl-1H-pyrazole-5-carboxamide.

In the title compound, C(24)H(21)ClN(4)O(2), the pyrazole ring makes dihedral angles of 7.70 (11), 89.17 (11) and 40.68 (11)° with the phenyl, pyridine and ethoxy-phenyl rings, respectively. There are some intra-molecular C-H⋯O and C-H⋯π bonds giving rigidity to the mol-ecule, while weak inter-molecular N-H⋯N and C-H⋯π hydrogen bonds link the mol-ecules into a two-dimensional structure.

Synthesis and discovery of autophagy inducers for A549 and H460 lung cancer cells, novel 1-(2'-hydroxy-3'-aroxypropyl)-3-aryl-1H-pyrazole-5-carbohydrazide derivatives.

A series of novel 1-(2'-hydroxy-3'-aroxypropyl)-3-aryl-1H-pyrazole-5-carbohydrazide derivatives were synthesized, and the effects of the compounds on A549 cell growth were investigated. The results showed that all of the 1-(2'-hydroxy-3'-aroxypropyl)-3-aryl-1H-pyrazole-5-carbohydrazide derivatives 2 could inhibit the growth of A549 cells in dosage- and time-dependent manners. Typically, compound 2a and 2d induced A549 cells to autophagy but did not cause apoptosis and necrosis in the cells, and 2d had the most autophagy inducing effect in H460 cells. More importantly, 2a and 2d did not inhibit the growth of HUVEC cells.

Synthesis and preliminary biological evaluation of novel pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives as potential agents against A549 lung cancer cells.

A series of novel pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives were synthesized by the reaction of ethyl 3-aryl-1-(2-bromoethyl)-1H-pyrazole-5-carboxylate and amine in the general heating condition and microwave-assisted condition. The structures of the compounds were determined by IR, (1)H NMR and mass spectroscopy, in addition, representative single-crystal structures were characterized by using X-ray diffraction analysis. Preliminary biological evaluation showed that the compounds could inhibit the growth of A549 cells in dosage- and time-dependent manners. The study on structure-activity relationships showed that compounds with 4-chlorophenyl group at pyrazole moiety, such as 5-benzyl-2-(4-chlorophenyl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one (3o) had much more inhibitory effects. Compound 3o was the most effective small molecule in inhibiting A549 cell growth and might perform its action through modulating autophagy.

N-Benzyl-2-(2,6-dichloro-phen-oxy)-acetamide.

The structure determination of the title compound, C(15)H(13)Cl(2)NO(2), was undertaken as part of a project on the inter-action of small mol-ecules with proteins. In the crystal structure, the dihedral angle between the two aryl rings is 40.71 (11)°. The mol-ecules are connected via N-H⋯O hydrogen bonding into chains, which extend in the direction of the b axis.

N-Cyclo-hexyl-2-(2,3-dichloro-phen-oxy)acetamide.

In the crystal structure of title compound, C(14)H(17)Cl(2)NO(2), the cyclo-hexyl ring is in a chair conformation and the mol-ecules are connected via N-H⋯O hydrogen bonding into chains.

N-Cyclo-hexyl-2-(2,3-dichloro-phenyl-sulfan-yl)acetamide.

In the crystal structure of title compound, C(14)H(17)Cl(2)NOS, the cyclo-hexyl ring has a chair conformation and connects with an equatorial N atom. Mol-ecules are connected via N-H⋯O hydrogen bonds into chains.

N-Benzyl-2-(2,4-dichloro-phen-oxy)acetamide.

In the title compound, C(15)H(13)Cl(2)NO(2), the dihedral angle between the aromatic rings is 27.17 (11)°. In the crystal the molecules are linked by N-H⋯O hydrogen bonds.

N-Benzyl-2-(2-chloro-4-methyl-phen-oxy)acetamide.

The structure determination of the title compound, C(16)H(16)ClNO(2), was performed as part of a project on the inter-actions between small organic mol-ecules and proteins. In the crystal structure, the dihedral angle between the two aromatic rings is 16.14 (12)°. The molecules are connected via N-H⋯O hydrogen bonding into chains, which extend in the direction of the b axis.

Ethyl 5-(ethoxy-carbon-yl)-3-(4-methoxy-phen-yl)-1H-pyrazole-1-acetate.

In the title compound, C(17)H(20)N(2)O(5), all bond lengths and angles show normal values. The dihedral angle between the pyrazole ring and the benzene ring is 6.98 (11)°. The mol-ecules are linked by inter-molecular C-H⋯π inter-actions.

1-(2-Hydr-oxy-5-methoxy-phen-yl)ethan-1-one N-[(E)-1-(2-hydr-oxy-5-methoxy-phen-yl)ethyl-idene]hydrazone.

In the title mol-ecule, C(18)H(20)N(2)O(4), which resides on a crystallographic centre of inversion (at the centre of the N-N bond), all non-H atoms apart from the meth-oxy substituent are approximately coplanar. The structure displays intra-molecular O-H⋯N hydrogen bonding.

Microwave-assisted synthesis, crystal structure of pyrazolo[1,5-a]pyrazin-4(5H)-ones and their selective effects on lung cancer cells.

A series of novel pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives with hydrophilic group was synthesized under general heating condition and microwave-assisted condition. The structures of compounds were determined by IR, 1H NMR and HRMS, moreover, representative crystal structures were characterized by using X-ray diffraction analysis. Preliminary biological evaluation showed that some compounds could inhibit the growth of A549, H322 and H1299 cells in dosage dependent manners. The compounds could inhibit growth of A549, H322 and H1299 cells in different mechanism. Compounds 3e-h inhibited growth of A549 cells by inducing a strong G1-phase arrest. Whereas these compounds inhibited growth of H1299 and H322 cells by inducing apoptosis.

Design, synthesis, and preliminary biological evaluation of novel ethyl 1-(2'-hydroxy-3'-aroxypropyl)-3-aryl-1H-pyrazole-5-carboxylate.

We synthesized a series of novel small molecules, ethyl 1-(2'-hydroxy-3'-aroxypropyl)-3-aryl-1H-pyrazole-5-carboxylate derivatives 3a-3o, by the reaction of ethyl 3-aryl-1H-pyrazole-5-carboxylate with 2-aryloxymethylepoxide in the presence of potassium carbonate at refluxing in acetonitrile in moderate or excellent yields. We investigated the effects of all the compounds on A549 cell growth. The results showed that 15 compounds could suppress A549 lung cancer cell growth. Among them, compound 3i was the most effective small molecule in inhibiting A549 cell growth. Compound 3f might most effectively induce A549 cell differentiation. Compound 3g remarkably induced cellular vacuolation.