Synthesis, Molecular Characterization, Biological and Computational Studies of New Molecule Contain 1,2,4-Triazole, and Coumarin Bearing 6,8-Dimethyl

Synthesis 4-(((4-ethyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl)thio)methyl)-6,8-dimethyl-coumarin and spectral analysis is carried out using the FT-IR and NMR with the help of quantum chemical calculation by DFT/6-311(d,p). The molecular electrostatic potentials and frontier molecular orbitals of the title compound were carried out at the B3LYP/6-311G(d,p) level of theory. Antimicrobial, antioxidant activity, and In vitro cytotoxic for cell lines were observed. The result shows that the theoretical vibrational frequencies, 1H-NMR and 13C-NMR chemical shift, agree with experimental data. In vitro studies showed that antimicrobial activity was weak, particularly against bacteria such as E. coli, S. aureus, P. aeruginosa, and B. cereus. The test compound's oxidative stress index (OSI) has appeared as 0.079 ± 0.214 in antioxidant and oxidant capacity studies. The compound did not cause a harmful cytotoxic effect on healthy cell lines and showed no potential for anticancer activity on cancerous cell lines such as MCF-7 and MKN-45.

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In Vitro Evaluation of Chitosan Induced Cytotoxicity against Cancerous Cell lines: MCF-7, Saos-2 and HeLa

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190507113949 ◽

2019 ◽

Vol 19 ◽

Author(s):

Zeinab Abedian ◽

Niloofar Jenabian ◽

Ali Akbar Moghadamnia ◽

Ebrahim Zabihi ◽

Roghayeh Pourbagher ◽

...

Keyword(s):

Flow Cytometry ◽

Cell Lines ◽

Anticancer Agents ◽

Fibroblast Cells ◽

Apoptosis Induction ◽

Cytotoxic Effects ◽

Cancerous Cell ◽

Significant Concentration ◽

Mcf 7

Objective/ Background: Cancer is still the most common cause of morbidity in world and new powerful anticancer agents without severe side effects from natural sources is important. Methods: The evaluation of cytotoxicity and apoptosis induction was carried out in MCF-7,HeLa and Saos-2 as cancerous cell lines with different histological origin and human fibroblast served as control normal cell. The cells were treated with different concentrations of chitosan and the cytotoxicity was determined using MTT assay after 24, 48 and 72 h .The mode of death was evaluated by flow cytometry . Results: While both types of chitosan showed significant concentration-dependently cytotoxic effects against the three cancerous cell lines, fibroblast cells showed somehow more compatibility with chitosan. On the other hand, there were no significant differences between LMWC and HMWC cytotoxicity in all cell lines. The flow cytometry results showed the apoptosis pattern of death more in Saos-2 and HeLa while necrosis was more observable with MCF7. Also higher viability with both types of chitosan was seen in fibroblast as normal cells Conclusion: Chitosan shows anticancerous effect against 3 cancerous cell lines, while it is compatible with normal diploid fibroblast cells. Furthermore, it seems that the molecular weight of chitosan does not affect its anticancerous property.

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Συνδυασμός αντιβιοτικών με μεταλλικά ιόντα σε μια ενιαία οντότητα για στοχευμένη θεραπεία στον καρκίνο του μαστού

10.12681/eadd/49610 ◽

2021 ◽

Author(s):

Μαρία Χρυσούλη

Keyword(s):

Escherichia Coli ◽

Staphylococcus Aureus ◽

Staphylococcus Epidermidis ◽

Artemia Salina ◽

E Coli ◽

Ft Ir ◽

Cetrimonium Bromide ◽

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Συντέθηκε και χαρακτηρίστηκε πλήρως το νέο μεταλλοθεραπευτικό Ph2Sn(CIP)2 (CIPTIN) (HCIP = σιπροφλοξασίνη) από την αντίδραση του εμπορικά διαθέσιμου αντιβιοτικού υδροχλωριωμένη σιπροφλοξασίνη (HCIP·HCl) με το άλας του διφαινυλοδιχωροκασσιτέρου (Ph2SnCl2 DPTD). Επίσης απομονώθηκε και λύθηκε η κρυσταλλική δομή του εσωτερικού άλατος της σιπροφλοξασίνης (HCIP). Στη συνέχεια, με σκοπό να ενισχυθεί η υδατοδιαλυτότητα και κατ’ επέκταση η βιολογική δράση και η βιοδιαθεσιμότητα του CIPTIN και του DPTD, παρασκευάστηκαν τα μικκύλια SLS@CIPTIN, CTAB@CIPTIN, SLS@DPTD και CTAB@DPTD (SLS = sodium lauryl sulphate and CTAB = cetrimonium bromide).Το νέο μεταλλοθεραπευτικό χαρακτηρίστηκε σε στερεά κατάσταση με μελέτη της περίθλασης ακτίνων Χ (XRD), ανάλυση της περίθλασης ακτίνων Χ κόνεως (XRPD), φασματοσκοπία φθορισμού ακτίνων Χ (XRF), φασματοσκοπία υπερύθρου (FT-IR), φασματοσκοπία 119Sn Mössbauer, θερμική ανάλυση (TG / DTA), διαφορική θερμιδομετρία σάρωσης (DSC), μελέτη του σημείου τήξεως και σε υγρή κατάσταση με φασματοσκοπία υπεριώδους-ορατού (UV-VIS), φασματοσκοπία πυρηνικού μαγνητικού συντονισμού πρωτονίου (1Η-NMR) και με φασματοσκοπία μάζας ιοντικού ηλεκτροψεκασμού (ESI-MS). Ο χαρακτηρισμός των μικκυλίων πραγματοποιήθηκε με μελέτη του σημείου τήξεως, με φασματοσκοπία φθορισμού ακτίνων Χ, υπερύθρου, 119Sn Mössbauer, πυρηνικού μαγνητικού συντονισμού πρωτονίου, με θερμική ανάλυση και με διαφορική θερμιδομετρία σάρωσης. Η αντιπολλαπλασιαστική δράση του CIPTIN και των μικκυλίων SLS@CIPTIN, CTAB@CIPTIN, SLS@DPTD και CTAB@DPTD, μελετήθηκε έναντι των ανθρώπινων καρκινικών κυτταρικών σειρών του μαστού: MCF-7 (εκφράζουν οιστρογονικούς υποδοχείς) και MDA-MB-231 (δεν εκφράζουν οιστρογονικούς υποδοχείς). Η τοξικότητα των ενώσεων ελέγχθηκε in vitro έναντι φυσιολογικών κυττάρων MRC-5 και in vivo με το ζωικό μοντέλο Artemia Salina, ενώ η πιθανή γονοτοξικότητα ελέγχθηκε in vitro με μελέτη των μικροπυρηνίσκων και in vivo με τη βοήθεια του μοντέλου Allium cepa. Οι μελέτες της μορφολογίας των κυττάρων, του κυτταρικού κύκλου και του κατακερματισμού του πυρηνικού DNA που πραγματοποιήθηκαν σε κύτταρα MCF-7 μετά την επώασή τους με τις ενώσεις που συντέθηκαν και αποδεικνύουν ότι οι νέες ενώσεις προκαλούν κυτταρικό θάνατο μέσω απόπτωσης. Ταυτόχρονα, οι μελέτες της διαπερατότητας της μιτοχονδριακής μεμβράνης αποκάλυψαν ότι οι νέες ενώσεις προκαλούν απόπτωση μέσω της επίδρασής τους στα μιτοχονδριακά μονοπάτια των κυττάρων. Επιπλέον, μελετήθηκε η αλληλεπίδραση των ενώσεων με το DNA, καθώς και η αντιμικροβιακή δράση των νέων ενώσεων έναντι των βακτηριακών στελεχών Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) και Staphylococcus epidermidis (S. epidermidis), με προσδιορισμό της ελάχιστης ανασταλτικής συγκέντρωσης (MIC), της ελάχιστης βακτηριοστατικής συγκέντρωσης (MBC), των ζωνών αναστολής (IZs) και της επίδρασης των ενώσεων στο σχηματισμό βακτηριακού βιοφίλμ. Τέλος, διερευνήθηκε η σχέση μεταξύ της αντικαρκινικής και της αντιμικροβιακής δράσης που επιδεικνύουν οι βιοδραστικές ενώσεις.

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(Substituted)-benzo[b]thiophene-4-carboxamide Synthesis and Antiproliferative Activity Study

Letters in Drug Design & Discovery ◽

10.2174/1570180815666181004114125 ◽

2020 ◽

Vol 17 (5) ◽

pp. 563-573 ◽

Cited By ~ 2

Author(s):

Chandrakant Dhondiram Pawar ◽

Dattatraya Navnath Pansare ◽

Devanand Baburao Shinde

Keyword(s):

Anticancer Activity ◽

Cell Lines ◽

Proliferative Activity ◽

Thiophene Ring ◽

Amide Group ◽

Peptide Coupling ◽

Ic50 Value ◽

Important Building Block ◽

Mcf 7

Background: Thiophene ring forms important building block in medicinal chemistry. Literature reveals that thiophene ring in combination with different groups shows different activity. By keeping these things in mind we have designed and synthesized a new series of amide and sulfonamide coupled thiophene. A series of novel substituted 3-sulfamoylbenzo[b]thiophene-4- carboxamide molecules containing sulfonamide and amide group were designed, synthesized and used for anti-proliferative activity study. Methods: The final compounds 16-36 were synthesized by using series of reactions comprising sulfonation, sulfonamide coupling, hydrolysis and peptide coupling. The yields of compounds 16- 36 are in the range of 90-98%. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR, 13C NMR, LCMS and the purity was checked through HPLC analysis. The compounds were further tested for their in vitro anticancer activity against a series of cell lines A549, HeLa, MCF-7 and Du-145. Results: The intermediates 8-13, 15 and final compounds 16-36 were synthesized in good yields. The synthesized compounds were further tested for their anticancer activity and most of compounds showed moderate to good anticancer activity against all four cell lines. Conclusion: We have synthesized 21 compounds and were screened for anticancer activity against MCF-7, HeLa, A-549 and Du-145 cancer cell lines. Most of the compounds were active for tested cell lines with IC50 value in the range of 1.81 to 9.73 μM. The compounds 18, 19, 21, 25, 30, 31 and 33 are most active in cell line data with IC50 value in the range of 1.81 to 2.52 μM.

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In Vitro Antitumor Evaluation of Some Hybrid Molecules Containing Coumarin and Quinolinone Moieties

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190930143856 ◽

2020 ◽

Vol 19 (16) ◽

pp. 2010-2018

Author(s):

Youstina W. Rizzk ◽

Ibrahim M. El-Deen ◽

Faten Z. Mohammed ◽

Moustafa S. Abdelhamid ◽

Amgad I.M. Khedr

Keyword(s):

Cell Cycle ◽

Cell Lines ◽

Cancer Cell ◽

Anticancer Agents ◽

Topoisomerase Ii ◽

Cancer Cell Lines ◽

Bax Protein ◽

Hybrid Molecules ◽

Mcf 7

Background: Hybrid molecules furnished by merging two or more pharmacophores is an emerging concept in the field of medicinal chemistry and drug discovery. Currently, coumarin hybrids have attracted the keen attention of researchers to discover their therapeutic capability against cancer. Objective: The present study aimed to evaluate the in vitro antitumor activity of a new series of hybrid molecules containing coumarin and quinolinone moieties 4 and 5 against four cancer cell lines. Materials and Methods: A new series of hybrid molecules containing coumarin and quinolinone moieties, 4a-c and 5a-c, were synthesized and screened for their cytotoxicity against prostate PC-3, breast MCF-7, colon HCT- 116 and liver HepG2 cancer cell lines as well as normal breast Hs-371 T. Results: All the synthesized compounds were assessed for their in vitro antiproliferative activity against four cancer cell lines and several compounds were found to be active. Further in vitro cell cycle study of compounds 4a and 5a revealed MCF-7 cells arrest at G2 /M phase of the cell cycle profile and induction apoptosis at pre-G1 phase. The apoptosis-inducing activity was evidenced by up-regulation of Bax protein together with the downregulation of the expression of Bcl-2 protein. The mechanism of cytotoxic activity of compounds 4a and 5a correlated to its topoisomerase II inhibitory activity. Conclusion: Hybrid molecules containing coumarin and quinolinone moieties represents a scaffold for further optimization to obtain promising anticancer agents.

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New Ferrocene Compounds as Selective Cyclooxygenase (COX-2) Inhibitors: Design, Synthesis, Cytotoxicity and Enzyme-inhibitory Activity

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666171003145533 ◽

2018 ◽

Vol 18 (2) ◽

pp. 295-301 ◽

Cited By ~ 8

Author(s):

Shabnam Farzaneh ◽

Elnaz Zeinalzadeh ◽

Bahram Daraei ◽

Soraya Shahhosseini ◽

Afshin Zarghi

Keyword(s):

Cell Lines ◽

Inhibitory Activity ◽

Fibroblast Cell ◽

Breast Cancer Cell Lines ◽

Ferrocene Derivatives ◽

Cox 2 ◽

Cytotoxicity Effects ◽

Cox 2 Inhibitors ◽

Mcf 7

Background: Due to the astonishing properties of ferrocene and its derivatives, it has a broad application in diverse areas. Numerous ferrocene derivatives demonstrated anti-proliferative activity. Also COX-2, as a key isoenzyme for production of prostaglandins, is frequently overexpressed in various cancers. It is now recognized that COX-2 over expression promotes tumorigenic functions which can be suppressed by COX-2 inhibitors, a phenomenon useful for the preventing of tumor progression. The combination of COX-2 inhibitors with other anti-cancer or cancer prevention drugs may reduce their side effects in future cancer prevention and treatment. Objective: Owing to high anticancer potential of ferrocene derivatives and considerable COX-2 inhibitory and cytotoxicity effects of our previously synthesized chalcones, we decided to incorporate the ferrocenyl moiety into appropriate COX-2 inhibitor chalcone based scaffold, to evaluate COX-2 inhibitory activity as well as anticancer activities. Methods: Chalcones were synthesized via clasien-schmidt condensation of methylsulfonyl aldehyde and acetyl ferrocene. Further different amines with solvent free and ultra sound condition were reacted with chalcones to have different 1-ferrocenyl-3-amino carbonyl compounds. Docking study was carried out with Auto Dock vina software. All the newly-synthesized compounds were evaluated for their cyclooxygenase-2 (COX-2) inhibitory activity using chemiluminescent enzyme assays as well as cytotoxicity activity against MCF-7 and T47D and fibroblast cell lines by MTT assay. Results: In vitro COX-1/COX-2 inhibition studies demonstrated that all compounds were selective inhibitors of the COX-2 isozyme with IC50 values in the highly potent 0.05-0.12 µM range, and COX-2 selectivity indexes (SI) in the 148.3-313.7 range. These results indicated that either potency or selectivity of COX-2 inhibitory activity was affected by the nature and size of the substituents on C-3 of propane-1-one. Also anti-proliferative and toxicity activities of synthesized compounds against breast cancer cell lines MCF-7 and T47D and fibroblast cell lines showed that the synthesized compounds had mild to moderate cytotoxicity against MCT7 and T47D breast cancer cell lines at 10 µM concentration. In vitro COX-1/COX-2 inhibition studies and anticancer activity against MCF-7, identified 1-ferrocenyl-3-(4-methylsulfonylphenyl) propen-1-one as a potent compound (IC50 COX-2 = 0.05 µM, MCF-7: % inhibition (at concentration of 10 µM) = 32.7%), and also 1-ferrocenyl-3- (propan-1-amine)-3-(4-methylsulfonylphenyl) propan-1-one showed the most selectivity on COX-2 inhibition (selectivity index= 313.7). Conclusion: A novel group of ferrocene compounds, possessing a methyl sulfonyl COX-2 pharmacophore were synthesized to investigate the effect of different substituents on selectivity and potency of COX-2 inhibitory activity and their cytotoxicity effects. This study indicates that 1-ferrocenyl-3-amino carbonyl compounds having ferrocene motif and methyl sulfonyl COX-2 pharmacophore is a suitable scaffold to design COX-2 inhibitors and anti-cancer agents.

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Rapid bio-reduction of Trivalent aurum using in vitro Babchi leaf powder and its cytotoxicity against breast cancer MCF-7 cell lines

Applied Nanoscience ◽

10.1007/s13204-021-01958-6 ◽

2021 ◽

Author(s):

G. Siva ◽

S. Venkatesh ◽

G. Prem Kumar ◽

M. Muthukumar ◽

T. Senthil Kumar ◽

...

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

Leaf Powder ◽

Mcf 7

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Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity

Molecules ◽

10.3390/molecules26133923 ◽

2021 ◽

Vol 26 (13) ◽

pp. 3923

Author(s):

Adel A.-H. Abdel-Rahman ◽

Amira K. F. Shaban ◽

Ibrahim F. Nassar ◽

Dina S. EL-Kady ◽

Nasser S. M. Ismail ◽

...

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Lines ◽

Human Cancer Cell ◽

Molecular Docking Study ◽

Human Cancer Cell Lines ◽

Hct 116 ◽

Mcf 7

New pyridine, pyrazoloyridine, and furopyridine derivatives substituted with naphthyl and thienyl moieties were designed and synthesized starting from 6-(naphthalen-2-yl)-2-oxo-4-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile (1). The chloro, methoxy, cholroacetoxy, imidazolyl, azide, and arylamino derivatives were prepared to obtain the pyridine-−C2 functionalized derivatives. The derived pyrazolpyridine-N-glycosides were synthesized via heterocyclization of the C2-thioxopyridine derivative followed by glycosylation using glucose and galactose. The furopyridine derivative 14 and the tricyclic pyrido[3′,2′:4,5]furo[3,2-d]pyrimidine 15 were prepared via heterocyclization of the ester derivative followed by a reaction with formamide. The newly synthesized compounds were evaluated for their ability to in vitro inhibit the CDK2 enzyme. In addition, the cytotoxicity of the compounds was tested against four different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549). The CDK2/cyclin A2 enzyme inhibitory results revealed that pyridone 1, 2-chloro-6-(naphthalen-2-yl)-4-(thiophen-2-yl)nicotinonitrile (4), 6-(naphthalen-2-yl)-4-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (8), S-(3-cyano-6-(naphthaen-2-yl)-4-(thiophen-2-yl)pyridin-2-yl) 2-chloroethanethioate (11), and ethyl 3-amino-6-(naphthalen-2-yl)-4-(thiophen-2-yl)furo[2,3-b]pyridine-2-carboxylate (14) are among the most active inhibitors with IC50 values of 0.57, 0.24, 0.65, 0.50, and 0.93 µM, respectively, compared to roscovitine (IC50 0.394 μM). Most compounds showed significant inhibition on different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549) with IC50 ranges of 31.3–49.0, 19.3–55.5, 22.7–44.8, and 36.8–70.7 μM, respectively compared to doxorubicin (IC50 40.0, 64.8, 24.7 and 58.1 µM, respectively). Furthermore, a molecular docking study suggests that most of the target compounds have a similar binding mode as a reference compound in the active site of the CDK2 enzyme. The structural requirements controlling the CDK2 inhibitory activity were determined through the generation of a statistically significant 2D-QSAR model.

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In Vitro Cytotoxic Effects of Secondary Metabolites Present in Sarcopoterium Spinosum L.

Applied Sciences ◽

10.3390/app11115300 ◽

2021 ◽

Vol 11 (11) ◽

pp. 5300

Author(s):

Jozef Hudec ◽

Jan Mojzis ◽

Marta Habanova ◽

Jorge A. Saraiva ◽

Pavel Hradil ◽

...

Keyword(s):

Mammary Gland ◽

Ethyl Acetate ◽

Cytotoxic Activity ◽

Cell Lines ◽

Benzalkonium Chloride ◽

Ethanol Extract ◽

Cytotoxic Activities ◽

Sarcopoterium Spinosum ◽

Mcf 7

Sarcopoterium spinosum (L.) is a medicinal plant traditionally used for the treatment of various diseases including cancer in the Near- and Middle East. The fractions and constituents of the ethanol extract of S. spinosum were screened for in vitro cytotoxic activities on Jurkat (acute T-lymphoblastic leukemia), HeLa (cervical adenocarcinoma), MCF-7 (mammary gland adenocarcinoma), Caco-2 (human colorectal adenocarcinoma), and MDA-MB-231 (mammary gland adenocarcinoma) cell lines using the MTT (3-(dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The ethanol extract was subsequently re-extracted with ethyl acetate and in its sub-fraction obtained by column chromatography three compounds (stachydrine, benzalkonium chloride and rutine) were the first time identified by nuclear magnetic resonance (NMR) analyses. The most active subfraction showed cytotoxic activity against HeLa, MCF-7, and Caco-2 cell lines. The three compounds mentioned, as standards of high-performance liquid chromatography (HPLC) quality, were studied individually and in combination. Cytotoxic activity observed might be due to the presence of benzalkonium chloride and rutin. Benzalkonium chloride showed the strongest growth suppression effect against HeLa cells (IC50 8.10−7 M) and MCF-7 cells (IC50 5.10−6 M). The mixture of stachydrine and benzalkonium chloride allowed a synergistic cytotoxic effect against all tested cancer and normal cells to be obtained. Anti-cancer activity of the plant extract of S. spinosum remains under-investigated, so this research describes how the three major compounds identified in the ethyl acetate extract can exert a significant dose dependent in vitro cytotoxicity.

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Design, Synthesis and Biological Evaluation of Novel Benzothiazole Based [1,2,4]Triazolo[4,3-c]quinazoline Derivatives

Asian Journal of Chemistry ◽

10.14233/ajchem.2020.22453 ◽

2020 ◽

Vol 32 (3) ◽

pp. 580-586

Author(s):

Ranjit V. Gadhave ◽

Bhanudas S. Kuchekar

Keyword(s):

Biological Evaluation ◽

Bacterial Strains ◽

Active Compounds ◽

Design Synthesis ◽

Structural Modifications ◽

E Coli ◽

Chemical Structures ◽

Ft Ir ◽

Antioxidant Agent

A new series of N-(benzo[d]thiazol-2-yl)-[1,2,4]triazolo[4,3-c]quinazoline-5-carboxamide derivatives were synthesized by condensation of [1,2,4]triazolo[4,3-c]quinazoline-5-carboxylate derivatives with substituted benzothiazoles. The chemical structures of the synthesized compounds were confirmed by FT-IR, MS and 1H NMR spectra. Designed triazoloquinazoline derivatives were docked with oxido-reductase enzyme (PDB Code 4h1j) and DNA gyrase enzyme (PDB Code 3g75). Based on high binding affinity score, the best compound were selected for synthesis and subjected to in vitro antioxidant and antibacterial activity. Compounds 7a and 7d were found to be most active compounds as antioxidant agent among this series when compared with ascorbic acid. Compounds 7a, 7d and 7f were found to be most active compounds as an antibacterial agents among this series when compared with ciprofloxacin against bacterial strains such as S. aureus (ATCC 25923), E. coli (ATCC 25922) and P. aeruginosa (ATCC 27853). Study revealed that the most active compounds after structural modifications can be exploited as lead molecules for other pharmacological activities such as anti-inflammatory, anticancer and antidepressant activities.

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