SYNTHESIS OF 4-HYDROXY-3-(1-HYDROXY-2-(SUBSTITUTEDAMINO)ETHYL)-1-PHENYL/ METHYL QUINOLIN-2(1H)-ONE AS ANTICANCER AGENTS

Objective: The current work is concerned with the synthesis of a series of 4-hydroxy-3-(1-hydroxy-2-(substituted amino)ethyl)-1-phenyl/ methylquinolin-2(1H)-one[III-a(1-5)/III-b(1-5)] and evaluation of its in vitro anticancer activity.Methods: The starting material for linomide analogs was synthesized by following literature procedures. The carbonyl group was reduced to hydroxyl group using sodium borohydride, and the methyl group was brominated using bromine in acetic acid. Further bromine was nucleophilically substituted by primary amines. All the synthesized compounds were satisfactorily characterized by infrared, nuclear magnetic resonance, and mass spectral data. The synthesized compounds were tested for in vitro anticancer activity against MDA-MB cell line using the MTT assay method.Results: Among all the synthesized compounds, compound [III-a1;R=C6H5,R1=n-propylamine], [III-b1;R=CH3,R1=n-propylamine], and [III-b2;R=CH3,R1=methylamine] were found to be most cytotoxic with IC50 value=25 μg against the MDA-MB cell line.Conclusion: The results of screening studies concluded that compounds with (C6H5 at C1) and (long chain aliphatic and cyclic amines at C3) position of quinolin-2-one ring showed moderate activity.

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Synthesis, SAR, In-Silico appraisal and Anti-Microbial Study of substituted 2-aminobenzothiazoles derivatives

Current Computer - Aided Drug Design ◽

10.2174/1573409915666191210125647 ◽

2019 ◽

Vol 15 ◽

Cited By ~ 2

Author(s):

Devidas G. Anuse ◽

Suraj N. Mali ◽

Bapu R. Thorat ◽

Ramesh S. Yamgar ◽

Hemchandra K. Chaudhari

Keyword(s):

Antimicrobial Activity ◽

In Silico ◽

Docking Study ◽

Moderate Activity ◽

Molecular Docking Study ◽

Mass Spectral ◽

Gram Positive Bacteria ◽

Ft Ir ◽

In Silico Molecular Docking

Background: Antimicrobial resistance is major global health problem, which is being rapidly deteriorating the quality of human health. Series of substituted N-(benzo[d]thiazol-2-yl)-2-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)acetamide (3a-j) were synthesized from substituted N-(benzo[d]thiazol-2-yl)-2-chloroacetamide/bromopropanamide (2a-j) and 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole (2) and further evaluated for their docking properties and antimicrobial activity. Methods: All synthesized compounds were characterized by FT-IR, NMR and Mass spectral analysis. All compounds were allowed to dock against different antimicrobial targets having PDB ID: 1D7U and against common antifungal target having PDB ID: 1EA1. Results: The compounds 3d and 3h were showed good activity against Methicillin-resistant Staphylococcus aureus (MRSA, resistance Gram-positive bacteria). All synthesized compounds showed good to moderate activity against selected bacterial and fungal microbial strains. If we compared the actual in-vitro antimicrobial activity and in-silico molecular docking study, we found that molecules 3i and 3h were more potent than the others. Conclusion: Our current study would definitely pave the new way towards designing and synthesis of more potent 2-aminobenzothiazoles derivatives.

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Green Synthetic Protocol for (E)-1-Aryl-3-(2-morpholinoquinolin- 3-yl)prop-2-en-1-ones and Their Antimicrobial Activity

Asian Journal of Chemistry ◽

10.14233/ajchem.2019.21968 ◽

2019 ◽

Vol 31 (9) ◽

pp. 1895-1898

Author(s):

Relangi Siva Subrahmanyam ◽

Venkateswara Rao Anna

Keyword(s):

Antimicrobial Activity ◽

Spectral Data ◽

1H Nmr ◽

13C Nmr ◽

Mass Spectral Data ◽

In Vitro Antimicrobial Activity ◽

Mass Spectral ◽

Fungal Organisms

We report here an easy, efficient and green synthetic protocol for the (E)-1-aryl-3-(2-morpholinoquinolin-3-yl)prop-2-en-1-ones by the Claisen-Schmidt condensation of 2-morpholinoquinoline-3-carbaldehyde and different substituted acetophenones by using 1-butyl-3-methylimidazolium tetrafluoroborate (Bmim)BF4. The compounds were characterized by using 1H NMR, 13C NMR and mass spectral data and screened there in vitro antimicrobial activity against different bacterial and fungal organisms.

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SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF SOME NEWER BENZIMIDAZOLE DERIVATIVES BY MANNICH REACTION

INDIAN DRUGS ◽

10.53879/id.56.07.11797 ◽

2019 ◽

Vol 56 (07) ◽

pp. 16-22

Author(s):

N. Kumar ◽

D Pathak ◽

Keyword(s):

Salicylic Acid ◽

Elemental Analysis ◽

Mannich Reaction ◽

Anthelmintic Activity ◽

Biological Evaluation ◽

Benzimidazole Derivatives ◽

Good Activity ◽

Mass Spectral Data ◽

Mass Spectral

O-phenylenediamine and salicylic acid were used for the synthesis of 2-(1-(substituted phenylamino) methyl-1H benzo[d] imidazol-2-yl) phenol (2a-2h) derivatives by using various substituted aniline. In the first step, reaction of o-phenylenediamine and salicylic acid yielded 2-(1H-benzo[d]imidazol-2-yl) phenol (1), which on Mannich reaction with substituted aniline gave compounds (2a-2h). The structures of these compounds were characterized by IR, 1H NMR, mass spectral data and elemental analysis. Each analogue was tested in vitro for various types of pharmacological activity of this class of drugs including antibacterial, antifungal and anthelmintic activity. Among the synthesized compounds 2a act as vermifuge and no compound was found to be a vermicide. The compound 2c was found to be most active against E.coli and P. aeurigenosa and 2e be most active against B.subtilis and S.aureus. The derivative 2h shows good activity against C.albicans and A.niger.

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Structurally Simple Phenanthridine Analogues Based on Nitidine and Their Antitumor Activities

Molecules ◽

10.3390/molecules24030437 ◽

2019 ◽

Vol 24 (3) ◽

pp. 437

Author(s):

Shu-Qin Qin ◽

Lian-Chun Li ◽

Jing-Ru Song ◽

Hai-Yun Li ◽

Dian-Peng Li

Keyword(s):

Anticancer Agents ◽

Human Cancer ◽

A549 Cells ◽

Anticancer Activities ◽

Human Cancer Cell Lines ◽

Ic50 Value ◽

Ic50 Values ◽

Diphenyl Tetrazolium Bromide ◽

Conjugated Compounds

A series of novel structurally simple analogues based on nitidine was designed and synthesized in search of potent anticancer agents. The antitumor activity against human cancer cell lines (HepG2, A549, NCI-H460, and CNE1) was performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay in vitro. The results showed that some of them had good anticancer activities, especially derivatives with a [(dimethylamino)ethyl]amino side chain in the C-6 position. Planar conjugated compounds 15a, 15b, and 15c, with IC50 values of 1.20 μM, 1.87 μM, and 1.19 μM against CNE1 cells, respectively, were more active than nitidine chloride. Compound 15b and compound 15c with IC50 values of 1.19 μM and 1.37 μM against HepG2 cells and A549 cells demonstrated superior activities to nitidine. Besides, compound 5e which had a phenanthridinone core displayed extraordinary cytotoxicity against all test cells, particularly against CNE1 cells with the IC50 value of 1.13 μM.

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Steroidal glycoalkaloids fromSolanum nigrumtarget cytoskeletal proteins: anin silicoanalysis

PeerJ ◽

10.7717/peerj.6012 ◽

2019 ◽

Vol 7 ◽

pp. e6012 ◽

Cited By ~ 2

Author(s):

Rumana Ahmad

Keyword(s):

Binding Affinity ◽

Anticancer Agents ◽

Principal Component ◽

Cytoskeletal Proteins ◽

Hydroxyl Group ◽

Docking Analysis ◽

Drug Candidates ◽

Division Cell

BackgroundSolanum nigrum(black nightshade;S. nigrum), a member of family Solanaceae, has been endowed with a heterogeneous array of secondary metabolites of which the steroidal glycoalkaloids (SGAs) and steroidal saponins (SS) have vast potential to serve as anticancer agents. Since there has been much controversy regarding safety of use of glycoalkaloids as anticancer agents, this area has remained more or less unexplored. Cytoskeletal proteins like actin play an important role in maintaining cell shape, synchronizing cell division, cell motility, etc. and along with their accessory proteins may also serve as important therapeutic targets for potential anticancer candidates. In the present study, glycoalkaloids and saponins fromS. nigrumwere screened for their interaction and binding affinity to cytoskeletal proteins, using molecular docking.MethodsBioactivity score and Prediction of Activity Spectra for Substances (PASS) analysis were performed using softwares Molinspiration and Osiris Data Explorer respectively, to assess the feasibility of selected phytoconstituents as potential drug candidates. The results were compared with two standard reference drugs doxorubicin hydrochloride (anticancer) and tetracycline (antibiotic). Multivariate data obtained were analyzed using principal component analysis (PCA).ResultsDocking analysis revealed that the binding affinities of the phytoconstituents towards the target cytoskeletal proteins decreased in the order coronin>villin>ezrin>vimentin>gelsolin>thymosin>cofilin. Glycoalkaloid solasonine displayed the greatest binding affinity towards the target proteins followed by alpha-solanine whereas amongst the saponins, nigrumnin-I showed maximum binding affinity. PASS Analysis of the selected phytoconstituents revealed 1 to 3 violations of Lipinski’s parameters indicating the need for modification of their structure-activity relationship (SAR) for improvement of their bioactivity and bioavailability. Glycoalkaloids and saponins all had bioactivity scores between −5.0 and 0.0 with respect to various receptor proteins and target enzymes. Solanidine, solasodine and solamargine had positive values of druglikeness which indicated that these compounds have the potential for development into future anticancer drugs. Toxicity potential evaluation revealed that glycoalkaloids and saponins had no toxicity, tumorigenicity or irritant effect(s). SAR analysis revealed that the number, type and location of sugar or the substitution of hydroxyl group on alkaloid backbone had an effect on the activity and that the presence of α-L-rhamnopyranose sugar at C-2 was critical for a compound to exhibit anticancer activity.ConclusionThe present study revealed some cytoskeletal target(s) forS. nigrumphytoconstituents by docking analysis that have not been previously reported and thus warrant further investigations bothin vitroandin vivo.

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SYNTHESIS, CHARACTERIZATION AND IN VITRO STUDY OF ANTIBACTERIAL, ANTIFUNGAL ACTIVITIES OF SOME NOVEL DIHYDROPYRIMIDINTHIONE DERIVATIVES

Latin American Applied Research - An international journal ◽

10.52292/j.laar.2014.454 ◽

2014 ◽

Vol 44 (4) ◽

pp. 289-293

Author(s):

S. BALUJA ◽

S. CHANDA ◽

R. BHALODIA ◽

R. TALAVIYA

Keyword(s):

Biological Activities ◽

Wide Spectrum ◽

In Vitro Study ◽

Dimethyl Formamide ◽

Mass Spectral Data ◽

Antifungal Activities ◽

Mass Spectral ◽

Antibacterial And Antifungal Activities ◽

Antibacterial And Antifungal

Dihydropyrimidinthione is an important class of heterocyclic compounds which exhibits wide spectrum of biological activities. In the present study, some bio-active dihydropyrimidinthione derivatives have been synthesized and their characterization was done by IR, NMR and mass spectral data. The antibacterial and antifungal activities of synthesized compounds have also been studied in N,N-dimethyl formamide and Dimethyl sulfoxide.

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1H-Benzimidazole derivatives as mammalian DNA topoisomerase I inhibitors.

Acta Biochimica Polonica ◽

10.18388/abp.2007_3229 ◽

2007 ◽

Vol 54 (3) ◽

pp. 561-565 ◽

Cited By ~ 23

Author(s):

A Selcen Alpan ◽

H Semih Gunes ◽

Zeki Topcu

Keyword(s):

Topoisomerase I ◽

Biological Properties ◽

Benzimidazole Derivatives ◽

Type I ◽

Mass Spectral Data ◽

Dna Topoisomerase ◽

Mass Spectral ◽

Elemental Analyses ◽

Supercoil Relaxation

Benzimidazole is one of the most important heterocyclic groups manifesting various biological properties, such as antibacterial, antifungal, antimicrobial, antiprotozoal and antihelmintic activities. Several benzimidazole derivatives are also active as inhibitors of type I DNA topoisomerases. In this study, three 1H-benzimidazole derivatives with different electronic characteristics at position 5-, namely 5-chloro-4-(1H-benzimidazole-2-yl)phenol (Cpd I), 5-methyl-4-(1H-benzimidazole-2-yl)phenol (Cpd II) and 4-(1H-benzimidazole-2-yl)phenol (Cpd III), were synthesized and evaluated for their effects on mammalian type I DNA topoisomerase activity using quantitative in vitro plasmid supercoil relaxation assays. For the structure elucidation of the compounds, melting points, UV, IR, 1H NMR, 13C NMR, mass spectral data and elemental analyses were interpreted. Among the compounds, 5-methyl-4-(1H-benzimidazole-2-yl)phenol (Cpd II) manifested relatively potent topoisomerase I inhibition.

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In vitro Anti-Inflammation and Selective Cytotoxicity of Vero and HepG2 Cells by Phenolic Extract From Roots of Hermannia Geniculata Eckl and Zehl

Academic Journal of Life Sciences ◽

10.32861/ajls.66.61.66 ◽

2020 ◽

pp. 61-66

Author(s):

Adeniran Lateef Ariyo ◽

Ashafa Anofi Omotayo Tom

Keyword(s):

Anticancer Agents ◽

Hepg2 Cells ◽

Inflammatory Diseases ◽

Vero Cells ◽

Ic50 Value ◽

Phenolic Extract ◽

Anti Inflammatory ◽

Mtt Assays ◽

Anti Inflammation

Anti-inflammatory and in vitro cytotoxic effect of phenols of Hermannia geniculata (PoHG) on Vero and HepG2 cells was carried out using Soybean lipoxygenase and MTT assays. PoHG extract exhibited a commendable inhibition of 5-lipoxygenase enzyme with IC50 value of (150 ± 0.03) µg/mL which is similar to the IC50: (110± 0.01) µg/mL of the standard (indomethacin). However, the extract was non-toxic to Vero cells with LC50 value >1.00 mg/mL but highly toxic to HepG2 cells (LC50: 0.05 mg/mL). A decrease viability of HepG2 cells was observed with increase in the concentration of the extract. There was less than 5% viable HepG2 cells at PoHG concentration of 750 µg/mL. The selectivity index of (20.00 and 33.33) was recorded for PoHG extract and doxorubicin respectively. The anti-inflammatory activities of PoHG suggested that the phenols extract may be useful in the management of inflammatory diseases like artheriosclerosis, diabetes mellitus, rheumatoid arthritis and asthma. It is also safe for use while its antiproliferative activities can be exploited in search for anticancer agents.

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Evaluation of a Series of 9,10-Anthraquinones as Antiplasmodial Agents

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180607085102 ◽

2019 ◽

Vol 16 (3) ◽

pp. 353-363 ◽

Cited By ~ 1

Author(s):

Che Puteh Osman ◽

Nor Hadiani Ismail ◽

Aty Widyawaruyanti ◽

Syahrul Imran ◽

Lidya Tumewu ◽

...

Keyword(s):

Mode Of Action ◽

Hydrophobic Interactions ◽

Structural Characteristics ◽

Structural Features ◽

Antiplasmodial Activity ◽

Hydroxyl Groups ◽

Phytochemical Study ◽

Methyl Group ◽

Ic50 Value

Background: A phytochemical study on medicinal plants used for the treatment of fever and malaria in Africa yielded metabolites with potential antiplasmodial activity, many of which are Anthraquinones (AQ). AQs have similar sub-structure as naphthoquinones and xanthones, which were previously reported as novel antiplasmodial agents. Objective: The present study aimed to investigate the structural requirements of 9,10- anthraquinones with hydroxy, methoxy and methyl substituents to exert strong antiplasmodial activity and to investigate their possible mode of action. Methods: Thirty-one AQs were synthesized through Friedel-Crafts reaction and assayed for antiplasmodial activity in vitro against Plasmodium falciparum (3D7). The selected compounds were tested for toxicity and probed for their mode of action against β-hematin dimerization through HRP2 and lipid catalyses. The most active compounds were subjected to a docking study using AutoDock 4.2. Results: The active AQs have similar common structural characteristics. However, it is difficult to establish a structure-activity relationship as certain compounds are active despite the absence of the structural features exhibited by other active AQs. They have either ortho- or meta-arranged substituents and one free hydroxyl and/or carbonyl groups. When C-6 is substituted with a methyl group, the activity of AQs generally increased. 1,3-DihydroxyAQ (15) showed good antiplasmodial activity with an IC50 value of 1.08 µM, and when C-6 was substituted with a methyl group, 1,3- dihydroxy-6-methylAQ (24) showed stronger antiplasmodial activity with an IC50 value of 0.02 µM, with better selectivity index. Compounds 15 and 24 showed strong HRP2 activity and mild toxicity against hepatocyte cells. Molecular docking studies showed that the hydroxyl groups at the ortho (23) and meta (24) positions are able to form hydrogen bonds with heme, of 3.49 Å and 3.02 Å, respectively. Conclusion: The activity of 1,3-dihydroxy-6-methylAQ (24) could be due to their inhibition against the free heme dimerization by inhibiting the HRP2 protein. It was further observed that the anthraquinone moiety of compound 24 bind in parallel to the heme ring through hydrophobic interactions, thus preventing crystallization of heme into hemozoin.

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Synthesis and In Vitro Antibacterial and Antifungal Evaluation of Quinoline Analogue Azetidin and Thiazolidin Derivatives

International Letters of Chemistry Physics and Astronomy ◽

10.18052/www.scipress.com/ilcpa.39.195 ◽

2014 ◽

Vol 39 ◽

pp. 195-210 ◽

Cited By ~ 4

Author(s):

Shraddha M. Prajapati ◽

Rajesh H. Vekariya ◽

Kinjal D. Patel ◽

Shyamali N. Panchal ◽

Hitesh D. Patel ◽

...

Keyword(s):

Gram Negative Bacteria ◽

Aspergillus Clavatus ◽

Dilution Technique ◽

Mass Spectral Data ◽

Mass Spectral ◽

Gram Positive Bacteria ◽

H Nmr ◽

Antibacterial And Antifungal ◽

Broth Dilution

A library of quinoline analog two novel series of azetidin (SH1-5) and thiazolidin (SHa-e) derivatives were designed and synthesized with simple and eco-friendly methodologies. The structures of the compounds were elucidated with the aid of elemental analysis, IR, 1H-NMR and mass spectral data. These novel synthesized compounds were evaluated for antibacterial activity against two gram-positive bacteria (Staphylococcus aureus, Staphylococcus pyogenus) and two gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli). The title compounds were also studied for their antifungal activity with Candida albicans, Aspergillus niger, Aspergillus clavatus using the broth dilution technique. Most of the compounds were the best bio-active desired antibacterial analog with less MIC value against different tested strains.

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