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1.
Carbohydr Res ; 528: 108811, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37094532

ABSTRACT

A novel three-component strategy has been developed for the synthesis of iminosugars in good to excellent yields. This is the first report on the Mannich type addition of cyclic 1,3-diketones to aza-acetal derived from hydroxy-γ-lactone and arylamine to produce a novel series of aza-sugars with high selectivity.


Subject(s)
Amines , Sugars , Stereoisomerism , Ketones , Ions
2.
Bioorg Med Chem Lett ; 30(16): 127304, 2020 08 15.
Article in English | MEDLINE | ID: mdl-32631524

ABSTRACT

A new series of 1,2,3-triazole tethered chalcone acetamide derivatives (7a-c &8a-r) have been synthesized in excellent yields and their structures were determined by analytical and spectral (FT-IR, 1H NMR, 13C NMR & HRMS) studies. The newly synthesized derivatives were evaluated for their cytotoxic activity against four human cancer cell lines, such as HeLa (Human cervical cancer), A549 (Human alveolar adenocarcinoma), MCF-7 (Human breast adenocarcinoma) and SKNSH (Human brain cancer). Among them, compound 7c exhibited good anti-proliferation activity with HeLa (IC50 7.41 + 0.8 µM), SKNSH (IC50 8.68 + 1.1 µM), MCF-7 (IC50 9.76 + 1.3 µM) and MDA-MB-231, while compounds 7a and 7b showed promising anti-proliferation against above four human cancer cell lines with IC50 7.95-11.62 µM, respectively, compared with the standard drug Doxorubicin. We explored the probable key active site and binding mode interactions in HDAC8 (PDB ID:3SFH) and EHMT2 (PDB ID:3K5K) proteins. The docking results are complementary to the experimental observations.


Subject(s)
Acetamides/pharmacology , Antineoplastic Agents/pharmacology , Chalcone/pharmacology , Triazoles/pharmacology , Acetamides/chemical synthesis , Acetamides/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Chalcone/chemical synthesis , Chalcone/chemistry , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Structure-Activity Relationship , Triazoles/chemical synthesis , Triazoles/chemistry
3.
Bioorg Med Chem Lett ; 27(23): 5158-5162, 2017 12 01.
Article in English | MEDLINE | ID: mdl-29103973

ABSTRACT

A series of substituted triazole functionalized 2H-benzo[b][1,4]oxazin-3(4H)-ones were synthesized by employing click chemistry and further characterized based on 1H NMR, 13C NMR, IR and mass spectral studies. All the synthesized derivatives were screened for their in vitro antimicrobial activities. Further, molecular docking studies were accomplished to explore the binding interactions between 1,2,3-triazol-4-yl-2H-benzo[b][1,4]oxazin-3(4H)-one and the active site of Staphylococcus aureus (CrtM) dehydrosqualene synthase (PDB ID: 2ZCS). These docking studies revealed that the synthesized derivatives showed high binding energies and strong H-bond interactions with the dehydrosqualene synthase validating the observed antimicrobial activity data. Based on antimicrobial activity and docking studies, the compounds 9c, 9d and 9e were identified as promising antimicrobial leads.


Subject(s)
Anti-Infective Agents/chemistry , Oxazines/chemistry , Triazoles/chemistry , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/pharmacology , Bacterial Proteins/antagonists & inhibitors , Bacterial Proteins/metabolism , Binding Sites , Candida albicans/drug effects , Catalytic Domain , Farnesyl-Diphosphate Farnesyltransferase/antagonists & inhibitors , Farnesyl-Diphosphate Farnesyltransferase/metabolism , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria , Microbial Sensitivity Tests , Molecular Docking Simulation , Oxazines/chemical synthesis , Oxazines/pharmacology , Staphylococcus aureus/drug effects , Staphylococcus aureus/enzymology , Structure-Activity Relationship
4.
Bioorg Med Chem Lett ; 27(23): 5119-5121, 2017 12 01.
Article in English | MEDLINE | ID: mdl-29113761

ABSTRACT

A series of novel benzo[6,7]cyclohepta[1,2-b]pyridine-1,2,3-triazole hybrids (7a-j &8a-j) have been designed and synthesized in excellent yields by Huisgen's [3+2] cyclo addition reaction of 3-(azidomethyl)-2-methyl-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine (5) with various alkynes 6 in presence of copper sulphate and sodium ascorbate and their structures were confirmed by IR, 1H NMR, 13C NMR and HRMS. The newly synthesized compounds 7a-j &8a-j were evaluated for their in vitro anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC 27294). Among the compounds tested, the compounds 7i and 8g displayed most potent activity with MIC value of 1.56 µg/mL with low cytotoxicity.


Subject(s)
Antitubercular Agents/chemical synthesis , Drug Design , Triazoles/chemistry , Antitubercular Agents/pharmacology , Antitubercular Agents/toxicity , Cell Survival/drug effects , HEK293 Cells , Humans , Microbial Sensitivity Tests , Mycobacterium tuberculosis/drug effects , Pyridines/chemistry , Structure-Activity Relationship , Triazoles/pharmacology , Triazoles/toxicity
5.
Bioorg Med Chem Lett ; 27(24): 5481-5484, 2017 12 15.
Article in English | MEDLINE | ID: mdl-29089233

ABSTRACT

A novel synthetic protocol has been developed for the synthesis of 1,4-benzoxazinone-acetylphenylallyl quinazolin-4(3H)-one hybrids 7a-n by employing Pd-catalyzed CH arylation in presence of 5-10% phosphine ligand in good to excellent yields and evaluated for their anti-proliferative activity against three cancer cell lines such as A549 (lung), HeLa (cervical), MDA-MB-231 (breast). Compounds 7d, 7f, 7l and 7n exhibited promising anti-proliferative activity with GI50 values ranging from 0.37 to 2.73 µM respectively against A549, HeLa, and MDA-MB-231, while compound 7f showed significant activity against MDA-MB-231 with GI50 value 0.58 µM, 7j showed significant activity against A549 with GI50 value 0.32 µM and 7l showed significant activity against HeLa with GI50 value 0.37 µM. This is the first report on the synthesis and in vitro anti-proliferative evaluation of 1,4-benzoxazinone-acetylphenylallyl quinazolin-4(3H)-one hybrids.


Subject(s)
Antineoplastic Agents/chemistry , Benzoxazines/chemistry , Quinazolinones/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Design , Drug Screening Assays, Antitumor , HeLa Cells , Humans , Quinazolinones/chemical synthesis , Quinazolinones/pharmacology , Structure-Activity Relationship
6.
Bioorg Med Chem Lett ; 27(4): 792-796, 2017 02 15.
Article in English | MEDLINE | ID: mdl-28117204

ABSTRACT

A new series of 1-((9-chloro-2,3-dimethyl-6,7-dihydro-5H-benzo[7]annulen-8-yl)methoxy)-3-(4-phenylpiperzin-1-yl) propan-2-ols (6a-k) have been designed, synthesized and their structures were established by spectroscopic data (FT-IR, 1H NMR, 13C NMR, HRMS) and further confirmed by X-ray analysis. The newly synthesized compounds 6a-k were evaluated for their in vitro anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MDA-MB-231 (breast), A549 (lung) and MIAPACA (pancreatic). Among the compounds tested, the compound 6e displayed most potent activity against four cancer cell lines with GI50 values ranging from 0.010 to 0.097µM. The structure and anti-proliferative activity relationship was further supported by in silico molecular docking study of the active compounds against Colchicine binding site of ß-tubulin.


Subject(s)
Amino Alcohols/chemistry , Amino Alcohols/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Coumarins/chemistry , Piperazines/chemistry , Piperazines/pharmacology , A549 Cells , Binding Sites , Cell Line, Tumor , Cell Survival/drug effects , Colchicine/chemistry , Colchicine/metabolism , Colchicine/pharmacology , Coumarins/pharmacology , Crystallography, X-Ray , Drug Design , HeLa Cells , Humans , Molecular Conformation , Molecular Docking Simulation , Protein Structure, Tertiary , Tubulin/chemistry , Tubulin/metabolism
7.
Bioorg Med Chem Lett ; 27(2): 354-359, 2017 01 15.
Article in English | MEDLINE | ID: mdl-27964883

ABSTRACT

In an attempt to develop potential and selective anti-proliferative agents, a series of novel benzothiazine-piperazine derivatives 8a-i and 10a-g were synthesized by coupling of 2H-1,4-benzothiazin-3(4H)-one with various amines 7a-i and 9a-g in excellent yields and evaluated for their in vitro anti-proliferative activity against four cancer cell lines, HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma). In vitro inhibitory activity indicated that compounds 8a, 8d, 8g, 10a, 10b, 10e, 10f were found to be good anti-proliferative agents. Among them the derivatives 8g, 10e and 10f were found to be the most active members exhibiting remarkable growth inhibitory activity. Molecular docking was undertaken to investigate the probable binding mode and key active site interactions in HDAC8 and EHMT2 proteins. The docking results are complementary to the experimental results.


Subject(s)
Antineoplastic Agents/pharmacology , Peptides/pharmacology , Piperazines/pharmacology , Thiazines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Molecular Docking Simulation , Molecular Structure , Peptides/chemistry , Piperazine , Piperazines/chemistry , Structure-Activity Relationship , Thiazines/chemistry
8.
Eur J Med Chem ; 125: 400-410, 2017 Jan 05.
Article in English | MEDLINE | ID: mdl-27688193

ABSTRACT

A new series of 4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamide hybrids 8a-l have been designed and synthesized using peptide coupling agents with substituted N-phenyl piperazines and piperidines with good to excellent yields. The synthesized compounds were evaluated for their in vitro anti-proliferative activity against PANC 1, HeLa and MDA-MB-231. The compounds 8d, 8e, 8f, 8g, 8h and 8k exhibited considerable anti-proliferative activity with GI50 values ranging from 0.15 to 1.4 µM. The structure and anti-proliferative activity relationship was further supported by in silico molecular docking study of the active compounds against tubulin protein.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Proliferation/drug effects , Quinolones/chemistry , Quinolones/pharmacology , Tubulin Modulators/chemistry , Tubulin Modulators/pharmacology , Antineoplastic Agents/chemical synthesis , Cell Line, Tumor , Humans , Molecular Docking Simulation , Neoplasms/drug therapy , Neoplasms/metabolism , Piperazines/chemical synthesis , Piperazines/chemistry , Piperazines/pharmacology , Quinolones/chemical synthesis , Tubulin Modulators/chemical synthesis
9.
Bioorg Med Chem Lett ; 26(17): 4292-5, 2016 09 01.
Article in English | MEDLINE | ID: mdl-27476139

ABSTRACT

A series of benzosuberone bearing 1,2,3-triazoles were rationally designed and alkyl/aryl groups appended on 1,2,3-triazole derivatives 5a-o were synthesized using click chemistry and evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC27294). Compounds 5h (MIC: 3.125µg/mL) and 5l, 5m, 5o (MIC: 6.25µg/mL) exhibited promising hits. This is the first Letter on the synthesis and in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv of benzosuberone alkyl/aryl groups appended on 1,2,3-triazole derivatives.


Subject(s)
Coumarins/chemistry , Coumarins/pharmacology , Mycobacterium tuberculosis/drug effects , Triazoles/chemical synthesis , Antitubercular Agents/chemical synthesis , Antitubercular Agents/chemistry , Antitubercular Agents/pharmacology , Click Chemistry , Coumarins/chemical synthesis , Microbial Sensitivity Tests , Molecular Structure , Triazoles/chemistry , Triazoles/pharmacology
10.
Bioorg Med Chem Lett ; 26(13): 3014-3018, 2016 07 01.
Article in English | MEDLINE | ID: mdl-27209232

ABSTRACT

A new series of novel quinazolinones with allylphenyl quinoxaline hybrids 9a-n were efficiently synthesized in good yields by the reaction of 3-allyl-2-methylquinazolin-4(3H)-one (5a-n) with bromophenyl)quinoxaline (8) utilizing Pd catalyzed Heck-cross coupling and evaluated for anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma). Compounds 9a, 9e, 9g and 9h exhibited promising anti-proliferative activity with GI50 values ranging from 0.06 to 0.2µM against four cell lines, while compounds 9e and 9k showed significant activity against HeLa and MIAPACA cell lines and compounds 9b, 9d, 9h and 9j showed selective potency against IMR32 and MDA-MB-231 cell lines. This is the first report on the synthesis and in vitro anti-proliferative evaluation of E-2-(4-substituted)-3-(3-(4-(quinoxalin-2-yl)phenyl)allyl)quinazolin-4(3H)-ones (9a-n). Docking results indicate a sign of good correlation between experimental activity and calculated binding affinity (dock score), suggesting that these compounds could act as promising DNA intercalates.


Subject(s)
Antineoplastic Agents/pharmacology , Quinazolinones/pharmacology , Quinoxalines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , DNA/chemistry , Doxorubicin/pharmacology , Humans , Hydrogen Bonding , Intercalating Agents/chemical synthesis , Intercalating Agents/chemistry , Intercalating Agents/pharmacology , Molecular Docking Simulation , Paclitaxel/pharmacology , Quinazolinones/chemical synthesis , Quinazolinones/chemistry , Quinoxalines/chemical synthesis , Quinoxalines/chemistry , Structure-Activity Relationship
11.
Bioorg Med Chem Lett ; 26(3): 858-863, 2016 Feb 01.
Article in English | MEDLINE | ID: mdl-26748696

ABSTRACT

An efficient three-component protocol is described for the synthesis of benzo[6,7]cyclohepta[1,2-b]pyridine derivatives using ß-chloroacroleins, 1,3-dicarbonyls and ammonium acetate under catalyst free conditions by using ethanol as reaction media. The mild reaction conditions, operational simplicity and high yields are the advantages of this protocol and the broad scope of this one-pot reaction makes this procedure promising for practical usages. All the final compounds were screened for anti-inflammatory activity. Among the compounds tested, the compounds 5a, 5b, 5c, 5d, 5f, and 5k exhibited significant inhibition of IL-1ß and MCP-1 secretion as a measure of anti-inflammatory activity.


Subject(s)
Anti-Inflammatory Agents/chemistry , Pyridines/chemistry , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/pharmacology , Cell Line, Tumor , Chemokine CCL2/metabolism , Coumarins/chemistry , Crystallography, X-Ray , Humans , Interleukin-1beta/metabolism , Molecular Conformation , Monocytes/drug effects , Monocytes/metabolism , Pyridines/chemical synthesis
12.
Eur J Med Chem ; 96: 22-9, 2015.
Article in English | MEDLINE | ID: mdl-25874328

ABSTRACT

In an attempt to develop a new class of cardiovascular drugs, a series of novel carbazolyloxy phenylquinazoline derivatives 9a-g have been synthesized and evaluated as angiotensin converting enzyme (ACE) inhibitors. Most of these compounds exhibited activity as significant ACE inhibitors and three compounds (9b, 9c & 9e) showed maximum inhibitory potency in enzyme based assays. To render support to the experimental results, a series of quinazolinone derivatives were docked into active site of ACE and identified the probable binding modes compared to Lisinopril. Also we have identified common pharmacophore hypothesis (AAADDRR) among the best docked conformers of most potent compounds in a series of compounds. The most potent 9b, 9c, 9e compounds shared common active site with the Lisinopril binding site and retained the key active site residue interactions. The obtained results from pharmacological and molecular modeling studies can be utilized for further optimization of identified hits for selective inhibition of ACE.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Carbazoles/pharmacology , Drug Design , Peptidyl-Dipeptidase A/metabolism , Quinazolinones/pharmacology , Angiotensin-Converting Enzyme Inhibitors/chemical synthesis , Angiotensin-Converting Enzyme Inhibitors/chemistry , Carbazoles/chemical synthesis , Carbazoles/chemistry , Dose-Response Relationship, Drug , Humans , Models, Molecular , Molecular Structure , Quinazolinones/chemical synthesis , Quinazolinones/chemistry , Structure-Activity Relationship
13.
Bioorg Med Chem Lett ; 25(10): 2220-4, 2015.
Article in English | MEDLINE | ID: mdl-25827522

ABSTRACT

As an aspect of our ongoing research in search of new anti proliferative agents, a series of novel analogs of benzosuberone embedded with 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole moieties were synthesized in excellent yields (82-93%). All the newly synthesized compounds were characterized by (1)H NMR, (13)C NMR, ESI/LC-MS, HRMS and evaluated for their in vitro anti proliferative activity against four human cancer cell lines (cervical, breast, pancreatic and alveolar). Among the synthesized compounds, 4b, 6a, 7d and 7l showed potent anti proliferative activity with GI50 values range of 0.079-0.957µM against four human cancer cell lines. However, it was revealed that the compound 7d have shown very close GI50 value 0.079µM as compared with positive control of colchicine against cervical cancer cell line.


Subject(s)
Azoles/chemical synthesis , Azoles/pharmacology , Coumarins/chemical synthesis , Coumarins/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Molecular Structure , Oxadiazoles/chemical synthesis , Oxadiazoles/pharmacology , Thiadiazoles/chemical synthesis , Thiadiazoles/pharmacology , Triazoles/chemical synthesis , Triazoles/pharmacology
14.
Eur J Med Chem ; 94: 87-101, 2015 Apr 13.
Article in English | MEDLINE | ID: mdl-25757092

ABSTRACT

A series of novel quinazolinone hybrids were synthesized by employing click chemistry and evaluated for anti-proliferative activities against MCF-7, HeLa and K562 cell lines. Among these cell lines, HeLa cells were found to respond effectively to these quinazolinone hybrids with IC50 values ranging from 5.94 to 16.45 µM. Some of the hybrids (4q, 4r, 4e, 4k, 4t, 4w) with promising anti-cancer activity were further investigated for their effects on the cell cycle distribution. FACS analysis revealed the G1 cell cycle arrest nature of these hybrids. Further to assess the senescence inducing ability of these compounds, a senescence associated ß-gal assay was performed. The senescence inducing nature of these compounds was supported by the effect of hybrid (4q) on p16 promoter activity, the marker for senescence. Moreover, cells treated with most effective compound (4q) show up-regulation of p53, p21 and down-regulation of HDAC-1, HDAC-2, HDAC-5 and EZH2 mRNA levels. Docking results suggest that, the triazole nitrogen showed Zn(+2) mediated interactions with the histidine residue of HDACs.


Subject(s)
Apoptosis/drug effects , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylases/metabolism , Pyrroles/chemistry , Quinazolinones/pharmacology , Quinones/chemistry , Cell Cycle/drug effects , Cellular Senescence/drug effects , Click Chemistry , Enhancer of Zeste Homolog 2 Protein , HeLa Cells/drug effects , HeLa Cells/metabolism , Histone Deacetylase 1/chemistry , Histone Deacetylase 1/metabolism , Histone Deacetylase 2/chemistry , Histone Deacetylase 2/metabolism , Histone Deacetylase Inhibitors/chemistry , Histone Deacetylases/chemistry , Histone Deacetylases/genetics , Humans , Inhibitory Concentration 50 , K562 Cells/drug effects , MCF-7 Cells/drug effects , Molecular Docking Simulation , Polycomb Repressive Complex 2/chemistry , Polycomb Repressive Complex 2/metabolism , Quinazolinones/chemical synthesis , Quinazolinones/chemistry , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Proteins/metabolism
15.
Eur J Med Chem ; 89: 138-46, 2015 Jan 07.
Article in English | MEDLINE | ID: mdl-25462234

ABSTRACT

A series of novel 1,2,3-triazole-1,4-benzoxazine hybrids 5a-n were efficiently synthesized employing click chemistry approach and evaluated for anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma). Compounds 5n and 5g exhibited promising anti-proliferative activity with GI50 values ranging from 1.2 to 2.5 µM and 0.1-1.1 µM respectively against all cell lines, like HeLa, MDA-MB-231, MIAPACA and IMR32, while compound 5l showed significant activity against MDA-MB-231 and IMR32 with GI50 values ranging from 1.1 and 1.4 µM. This is the first report on the synthesis and in vitro anti-proliferative evaluation of 1,2,3-triazole-1,4-benzoxazine hybrids.


Subject(s)
Antineoplastic Agents/pharmacology , Benzoxazines/pharmacology , Drug Design , Triazoles/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Benzoxazines/chemical synthesis , Benzoxazines/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HeLa Cells , Humans , Molecular Structure , Structure-Activity Relationship , Triazoles/chemical synthesis , Triazoles/chemistry
16.
Bioorg Med Chem Lett ; 24(21): 5041-4, 2014 Nov 01.
Article in English | MEDLINE | ID: mdl-25264072

ABSTRACT

Two different series of novel analogues of benzosuberones (5a-m and 9a-w) tethered with hydrazone-hydrazides (functional group alterations: Head group to Tail group and vice versa) have been synthesized by the reaction of appropriate aldehydes with substituted hydrazides in excellent yields (87-94%) and their structures were confirmed by (1)H NMR, (13)C NMR, ESI-MS and HRMS. The newly synthesized compounds were evaluated for anti-proliferative activity against different human cancer cell lines (HeLa, MDA MB 231, MIAPACA and IMR32). Among the synthesized compounds, six compounds 5 a, 5 b, 5 d, 5 e, 5 f and 9 v exhibited potent anti-proliferative activity with GI50 values less than 0.01 µM against MIAPACA, MDA-MB-231 and IMR32 human cancer cell lines.


Subject(s)
Antineoplastic Agents/chemical synthesis , Coumarins/chemistry , Drug Design , Hydrazines/chemistry , Hydrazones/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Coumarins/chemical synthesis , Coumarins/pharmacology , HeLa Cells , Humans , Structure-Activity Relationship
17.
Eur J Med Chem ; 79: 260-5, 2014 May 22.
Article in English | MEDLINE | ID: mdl-24742385

ABSTRACT

A series of novel benzosuberone bearing coumarin moieties 5a-c have been synthesized and their structures were determined by analytical and spectral (FT-IR, (1)H NMR, (13)C NMR, HRMS) studies. The newly synthesized compounds were evaluated for their cytotoxicity against four human cancer cell lines, A549 (Human alveolar adenocarcinoma cell line), HeLa (Human cervical cancer cell line), MDA-MB-231 (Human breast adenocarcinoma cell line), MCF-7 (Human breast adenocarcinoma cell line) and normal cell line HEK293 (Human embryonic kidney cell line). Compound 5a exhibited promising cytotoxicity with IC50 values ranging from 3.35 to 16.79 µM against all the cancer cell lines like A549, HeLa, MCF-7 and MDA-MB-231, while compound 5c showed significant cytotoxicity against HeLa and MDA-MB-231 with IC50 values of 6.72 and 4.87, respectively.


Subject(s)
Antineoplastic Agents/pharmacology , Coumarins/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Coumarins/chemical synthesis , Coumarins/chemistry , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Female , HEK293 Cells , HeLa Cells , Humans , MCF-7 Cells , Models, Molecular , Molecular Structure , Structure-Activity Relationship
18.
Eur J Med Chem ; 71: 91-7, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24287557

ABSTRACT

Novel representative of the important group of biologically active benzosuberones bearing 2, 4-thiazolidenone moiety was synthesized as potential anticancer agents (6a-j). These compounds were synthesized in good yields from Knoevenagel condensation of compounds 2a-b with thiazolidenone derivatives 3a-e in the presence of sodium acetate and glacial acetic acid. The in vitro cytotoxicity of these compounds was evaluated against different human cancer cell lines (A549, HeLa, MDA-MB-231, MCF-7) and normal cell line, HEK293. Compound 6a exhibited promising cytotoxicity with IC50 values ranging from 2.98 to 13.34 µM against all the tested cancer cell lines, HeLa, A549, MCF-7 and MDA-MB-231, while compound 6g showed potent cytotoxicity against human breast adenocarcinoma cell line (MCF-7, IC50 value of 1.91 µM).


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cycloheptanes/chemistry , Cycloheptanes/pharmacology , Thiazoles/chemistry , Thiazoles/pharmacology , Antineoplastic Agents/chemical synthesis , Cell Line, Tumor , Cycloheptanes/chemical synthesis , HEK293 Cells , HeLa Cells , Humans , Models, Molecular , Neoplasms/drug therapy , Thiazoles/chemical synthesis
19.
Eur J Med Chem ; 69: 817-22, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24113366

ABSTRACT

A novel series of building blocks consisting of benzo[4,5]thiazolo[1,2-a]pyrimidine-3-carboxylate have been synthesized as potential anticancer compounds. These compounds were prepared from 2-aminobenzothiazole, benzaldehyde and ethyl acetoacetate in ethylene glycol by catalysing with TBAHS to give benzo[4,5]thiazo[1,2-a]pyrimidine derivative 4 followed by the formation of amide by reaction with several secondary amines in good yields. The cytotoxicity of these compounds was evaluated against human cancer cell lines in vitro (A549, HeLa, MDA-MB-231 and MCF-7). Compound 5b exhibited promising cytotoxicity with IC50 values of 0.58 and 1.58 µM specifically against human breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231, while compound 5a showed promising cytotoxicity against MDA-MB-231 (IC50 value of 5.01 µM).


Subject(s)
Antineoplastic Agents/pharmacology , Benzothiazoles/pharmacology , Pyrimidines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Benzothiazoles/chemical synthesis , Benzothiazoles/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HeLa Cells , Humans , MCF-7 Cells , Molecular Structure , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Structure-Activity Relationship
20.
Bioorg Med Chem Lett ; 21(14): 4138-40, 2011 Jul 15.
Article in English | MEDLINE | ID: mdl-21689936

ABSTRACT

A new series of 3-phenyl-N-[3-(4-phenylpiperazin-1yl)propyl]-1H-pyrazole-5-carboxamide derivatives were synthesized and investigated their anti-inflammatory activities using carrageenan-induced rat paw edema model in vivo. All the synthesized compounds were found to be potent anti-inflammatory agents.


Subject(s)
Amides/chemistry , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Pyrazoles/chemistry , Amides/chemical synthesis , Amides/therapeutic use , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Carrageenan/toxicity , Edema/chemically induced , Edema/drug therapy , Rats
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