Browse
Submit Data
Databases
API
Help

Dataset Information

41 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis, Antiprotozoal Activity, and Cheminformatic Analysis of 2-Phenyl-2H-Indazole Derivatives.

ABSTRACT: Indazole is an important scaffold in medicinal chemistry. At present, the progress on synthetic methodologies has allowed the preparation of several new indazole derivatives with interesting pharmacological properties. Particularly, the antiprotozoal activity of indazole derivatives have been recently reported. Herein, a series of 22 indazole derivatives was synthesized and studied as antiprotozoals. The 2-phenyl-2H-indazole scaffold was accessed by a one-pot procedure, which includes a combination of ultrasound synthesis under neat conditions as well as Cadogan's cyclization. Moreover, some compounds were derivatized to have an appropriate set to provide structure-activity relationships (SAR) information. Whereas the antiprotozoal activity of six of these compounds against E. histolytica, G. intestinalis, and T. vaginalis had been previously reported, the activity of the additional 16 compounds was evaluated against these same protozoa. The biological assays revealed structural features that favor the antiprotozoal activity against the three protozoans tested, e.g., electron withdrawing groups at the 2-phenyl ring. It is important to mention that the indazole derivatives possess strong antiprotozoal activity and are also characterized by a continuous SAR.

SUBMITTER: Rodriguez-Villar K

PROVIDER: S-EPMC8068258 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Synthesis and Biological Evaluation of 2H-Indazole Derivatives: Towards Antimicrobial and Anti-Inflammatory Dual Agents.

Project description:Indazole is considered a very important scaffold in medicinal chemistry. It is commonly found in compounds with diverse biological activities, e.g., antimicrobial and anti-inflammatory agents. Considering that infectious diseases are associated to an inflammatory response, we designed a set of 2H-indazole derivatives by hybridization of cyclic systems commonly found in antimicrobial and anti-inflammatory compounds. The derivatives were synthesized and tested against selected intestinal and vaginal pathogens, including the protozoa Giardia intestinalis, Entamoeba histolytica, and Trichomonas vaginalis; the bacteria Escherichia coli and Salmonella enterica serovar Typhi; and the yeasts Candida albicans and Candida glabrata. Biological evaluations revealed that synthesized compounds have antiprotozoal activity and, in most cases, are more potent than the reference drug metronidazole, e.g., compound 18 is 12.8 times more active than metronidazole against G. intestinalis. Furthermore, two 2,3-diphenyl-2H-indazole derivatives (18 and 23) showed in vitro growth inhibition against Candida albicans and Candida glabrata. In addition to their antimicrobial activity, the anti-inflammatory potential for selected compounds was evaluated in silico and in vitro against human cyclooxygenase-2 (COX-2). The results showed that compounds 18, 21, 23, and 26 display in vitro inhibitory activity against COX-2, whereas docking calculations suggest a similar binding mode as compared to rofecoxib, the crystallographic reference.

| S-EPMC6150295 | biostudies-literature

Design and Synthesis of New 6-Nitro and 6-Amino-3,3a,4,5-Tetrahydro-2H-Benzo[g]indazole Derivatives: Antiproliferative and Antibacterial Activity.

Project description:New substituted benzo[g]indazoles functionalized with a 6-nitro and 6-amino groups have been synthesized by the reaction of benzylidene tetralones with hydrazine in acetic acid. The resulting conformationally-constrained compounds were evaluated for their antiproliferative activity against selected cancer cell lines. The nitro-based indazoles 11a, 11b, 12a and 12b have shown IC50 values between 5-15 ?M against the lung carcinoma cell line NCI-H460. Moreover, the nitro compounds were tested for antibacterial activity where compounds 12a and 13b have shown MIC values of 250 and 62.5 ?g/mL against N. gonorrhoeae with no hemolytic activity in human red blood cells (RBC).

| S-EPMC6930490 | biostudies-literature

2-[2-(2,6-Di-chloro-benz-yloxy)-2-phenyl-eth-yl]-2H-indazole.

Project description:In the title compound, C22H18Cl2N2O, the indazole ring system is approximately planar [maximum deviation = 0.031 (2) Å], its mean plane is oriented at 3.17 (4) and 19.34 (4)° with respect to the phenyl and benzene rings. In the crystal, weak C-H⋯π inter-actions link the mol-ecules into supra-molecular chains running along the b-axis direction.

| S-EPMC3998539 | biostudies-literature

Design, Synthesis and Antitumor Activity of 1<i>H</i>-indazole-3-amine Derivatives.

Project description:A series of indazole derivatives were designed and synthesized by molecular hybridization strategy, and these compounds were evaluated the inhibitory activities against human cancer cell lines of lung (A549), chronic myeloid leukemia (K562), prostate (PC-3), and hepatoma (Hep-G2) by methyl thiazolyl tetrazolium (MTT) colorimetric assay. Among these, compound 6o exhibited a promising inhibitory effect against the K562 cell line with the IC50 (50% inhibition concentration) value of 5.15 µM, and this compound showed great selectivity for normal cell (HEK-293, IC50 = 33.2 µM). Moreover, compound 6o was confirmed to affect apoptosis and cell cycle possibly by inhibiting Bcl2 family members and the p53/MDM2 pathway in a concentration-dependent manner. Overall, this study indicates that compound 6o could be a promising scaffold to develop an effective and low-toxic anticancer agent.

| S-EPMC10218234 | biostudies-literature

rac-5-Acetyl-6-hy-droxy-3,6-dimethyl-4-phenyl-4,5,6,7-tetra-hydro-2H-indazole.

Project description:The title compound, C(17)H(20)N(2)O(2), is chiral but crystallizes in a centrosymmetric space group as a racemate, the relative configuration at the stereogenic centres being 2S*,3R*,4S*. The cyclo-hexane ring adopts a half-chair conformation while the pyrazole ring has an envelope conformation. The crystal packing displays inter-molecular O-H?N and N-H?O hydrogen bonding.

| S-EPMC3089358 | biostudies-literature

Design, synthesis, and antiprotozoal evaluation of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives.

Project description:A series of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline, and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives was designed, synthesised, and evaluated in vitro against three protozoan parasites (Plasmodium falciparum, Leishmania donovani, and Trypanosoma brucei brucei). Biological results showed antiprotozoal activity with IC50 values in the µM range. In addition, the in vitro cytotoxicity of these original molecules was assessed with human HepG2 cells. The quinoline 1c was identified as the most potent antimalarial candidate with a ratio of cytotoxic to antiparasitic activities of 97 against the P. falciparum CQ-sensitive strain 3D7. The quinazoline 3h was also identified as the most potent trypanosomal candidate with a selectivity index (SI) of 43 on T. brucei brucei strain. Moreover, as the telomeres of the parasites P. falciparum and Trypanosoma are possible targets of this kind of nitrogen heterocyclic compounds, we have also investigated stabilisation of the Plasmodium and Trypanosoma telomeric G-quadruplexes by our best compounds through FRET melting assays.

| S-EPMC6968685 | biostudies-literature

2-Allyl-7-nitro-2H-indazole.

Project description:The asymmetric unit of the title compound, C10H9N3O2, contains two independent mol-ecules linked by a C-H?N hydrogen bond. Each mol-ecule has a similar conformation, being built up from fused five- and six-membered rings, each linked to an ally and nitro group, respectively. The indazole ring system makes dihedral angles of 2.7?(2) and 2.2?(2)°, respectively, with the plane through the nitro group. The allyl group is nearly perpendicular to the indazole system, as indicated by the N-N-C-C torsion angles of -75.3?(2) and -82.2?(2)°, this being the most important difference between the conformations of the two mol-ecules. In the crystal, mol-ecules are linked by C-H?O and ?-? [inter-centroid distance = 3.6225?(8)?Å] inter-actions to form a three-dimensional network.

| S-EPMC3884280 | biostudies-literature

2,3-Dimethyl-6-nitro-2H-indazole.

Project description:In the mol-ecule of the title compound, C(9)H(9)N(3)O(2), the indazole ring system is almost planar [maximum deviation = 0.019?(3)?Å for the C atom bearing the nitro group]. In the crystal structure, inter-molecular C-H?O inter-actions link the mol-ecules into centrosymmetric dimers, forming R(2) (2)(18) ring motifs. Aromatic ?-? contacts between indazole rings [centroid-centroid distances = 3.632?(1) and 3.705?(1)?Å] may further stabilize the structure.

| S-EPMC2977458 | biostudies-literature

2-Methyl-6-nitro-2H-indazole.

Project description:In the title compound, C(8)H(7)N(3)O(2), the mol-ecular skeleton is almost planar with a maximum deviation of 0.0484 (9) Å for the methyl C atom. In the crystal, weak inter-molecular C-H⋯N and C-H⋯O hydrogen bonds help to establish the packing.

| S-EPMC3120619 | biostudies-literature

Recent Advances in Indazole-Containing Derivatives: Synthesis and Biological Perspectives.

Project description:Indazole-containing derivatives represent one of the most important heterocycles in drug molecules. Diversely substituted indazole derivatives bear a variety of functional groups and display versatile biological activities; hence, they have gained considerable attention in the field of medicinal chemistry. This review aims to summarize the recent advances in various methods for the synthesis of indazole derivatives. The current developments in the biological activities of indazole-based compounds are also presented.

| S-EPMC6278422 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data