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1.
Bioorg Chem ; 79: 277-284, 2018 09.
Article in English | MEDLINE | ID: mdl-29783098

ABSTRACT

DPP-IV "a moonlighting protein" has immerged as promising pathway to control Type 2 diabetes as well as found to play key role in earlier stages of cancer. Here we have reported design, synthesis and applications of aminocoumarin derivatives as DPP-IV inhibitors. Compounds have been synthesized and studied for their DPP-IV inhibition activity. Three compounds have shown moderate inhibition at 100 µM concentration. All compounds were also screened for their anticancer activity against A549 (Lung cancer cell line), MCF-7 (Breast cancer cell line) using MTT assay. One of the compounds has shown very good anticancer activity with IC50 value 24 ±â€¯0.1 nM against A549 cell line.


Subject(s)
Aminocoumarins/pharmacology , Antineoplastic Agents/pharmacology , Dipeptidyl Peptidase 4/metabolism , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Drug Design , Aminocoumarins/chemical synthesis , Aminocoumarins/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Dipeptidyl-Peptidase IV Inhibitors/chemical synthesis , Dipeptidyl-Peptidase IV Inhibitors/chemistry , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , MCF-7 Cells , Molecular Structure , Recombinant Proteins/metabolism , Structure-Activity Relationship
2.
Chem Biol Drug Des ; 92(1): 1279-1287, 2018 07.
Article in English | MEDLINE | ID: mdl-29575807

ABSTRACT

Herein we report design, synthesis, and anticancer activity of compounds 6a-h and 11a-j. Compounds 6a-f were designed based on 3-aminomethyl pyridine attached to different acetamide derivatives and in compounds 6g-h it was attached to coumarin moiety. Coumarin containing compounds 6g-h showed very poor anticancer activity against both A549 (Lungs cancer cell line), and MCF-7 (Breast cancer cell line) cell lines in MTT assay. Compounds 11a-j were designed as derivatives of 3-aminomethyl pyridine and 4-amino chalcones. A series of chalcone derivatives of 3-aminomethyl pyridine 11a-j have been synthesized and screened for their in vitro anticancer activity and DNA binding affinity. Most of the compounds showed very good antimitotic activity against A549 cell line as compared to fluorouracil. Compounds 11g and 11i were selected for DNA-binding studies as they showed excellent activity against cancer cell lines in MTT assay. CT-DNA binding affinity of compounds 11g and 11i have been investigated by UV based DNA titration and fluorescence emission study against DNA-EtBr complex. Interestingly, compound 11i has displayed excellent antiproliferative activity, with IC50 0.0067 ± 0.0002 µm, against MCF-7 cell line. Compound 11i has been studied for its cytotoxicity using MTT, LDH, as well as EtBr/AO assay and was found to induce apoptosis in the cancerous cell line.


Subject(s)
Antineoplastic Agents/chemistry , Chalcones/chemistry , DNA/chemistry , Drug Design , A549 Cells , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Proliferation/drug effects , Chalcones/metabolism , Chalcones/pharmacology , DNA/metabolism , Drug Screening Assays, Antitumor , Humans , MCF-7 Cells , Pyridines/chemistry , Structure-Activity Relationship
3.
Eur J Med Chem ; 90: 342-50, 2015 Jan 27.
Article in English | MEDLINE | ID: mdl-25437620

ABSTRACT

Type 2 diabetes (T2D) is a lifestyle disease affecting millions of people worldwide. Various therapies are available for the management of T2D and dipeptidyl peptidase-IV (DPP-IV) inhibition has emerged as a promising therapy for the treatment of type 2 diabetes (T2D). Here we report design, synthesis and in vitro efficacy of sulfonamide derivatives of pyrrolidine and piperidine as anti-diabetic agents. Amongst all the compounds synthesized in this series, 9a, is the most potent (IC50 = 41.17 nM).


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Drug Design , Hypoglycemic Agents/therapeutic use , Piperidines/therapeutic use , Pyrrolidines/therapeutic use , Sulfonamides/therapeutic use , Dose-Response Relationship, Drug , Humans , Hypoglycemic Agents/chemical synthesis , Hypoglycemic Agents/chemistry , Molecular Docking Simulation , Molecular Structure , Piperidines/chemistry , Pyrrolidines/chemistry , Structure-Activity Relationship , Sulfonamides/chemical synthesis , Sulfonamides/chemistry
4.
Eur J Med Chem ; 75: 77-81, 2014 Mar 21.
Article in English | MEDLINE | ID: mdl-24530493

ABSTRACT

We have synthesized various amide derivatives of benzodifuran-2-carboxylic acid from resorcinol. Reaction of 7-hydroxy-4-methylcoumarin with chloroacetone in anhydrous K2CO3 and dry acetone gave ether derivative of 7-hydroxy-4-methylcoumarin 3 which on reaction with N-bromosuccinimide in chloroform gave corresponding 3-bromo derivative 4. Cyclization of bromo derivative in 10% ethanolic KOH gave benzodifuran-2-carboxylic acid 5. This acid was converted into acid chloride using oxalyl chloride and then substituted with different amines in presence of base, triethylamine to give amide derivatives of benzodifuran-2-carboxylic acid 6. All compounds were screened for antimicrobial activity against two Gram positive bacteria Staphylococus aureus and Bacillus subtilis, two Gram negative bacteria E. coli and P. aeruginosa and one fungus Candida albicans.


Subject(s)
Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Benzofurans/chemistry , Benzofurans/pharmacology , Carboxylic Acids/chemistry , Carboxylic Acids/pharmacology , Amides/chemical synthesis , Amides/chemistry , Amides/pharmacology , Anti-Infective Agents/chemical synthesis , Bacterial Infections/drug therapy , Benzofurans/chemical synthesis , Candida albicans/drug effects , Candidiasis/drug therapy , Carboxylic Acids/chemical synthesis , Cyclization , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Microbial Sensitivity Tests
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