Synthesis and Biological Evaluation of Some Novel Substituted N-Benzylideneaniline Derivatives

ABSTRACT N-benzylideneaniline is a class of important compounds in medicinal and pharmaceutical field. Nbenzylideneaniline represents a model aromatic Schiff base and it is also a classic bioisoster of stilbene and resveratrol. Keeping in view the biological importance of N-benzylideneaniline we have synthesized some novel Nbenzylideneaniline derivatives. The prepared compounds were tested for their in vitro antibacterial, antifungal and antioxidant activity. (4-fluoro-benzylidene)-(3,5-dichloro-phenyl)-amine (5i) showed in vitro antibacterial activity comparable to that of the standard Penicillin against Escherichia coli. The results of the in vitro antifungal activity showed that most of the synthesized derivatives have proven their antifungal potential. The results of the in vitro antioxidant tests showed that most of the synthesized compounds showed moderate (%RSA >50%) to mild (%RSA >40%) radical scavenging activity

Sinteza, antitumorsko i citostatsko djelovanje derivata 6H-indolo[2,3-b]kinoksalina

Various 6-aralkyl-9-substituted-6H-indolo[2,3-b]quinoxalines were synthesized by reaction of 1,5-disubstituted 2,3-dioxo-2,3-dihydroindole with orthophenylene diamine. Appreciable anticancer activity of compounds 5b, 5d, 5g and 5l at various cell lines among 59 human tumor cell panels was observed. All the synthesized compounds were evaluated for cytostatic activity against human Molt 4/C8 and CEM T-lymphocytes as well as for murine L1210 leukemia cells. Compound 5h exhibited an IC50 of 71 μmol mL1 against Molt 4/C8 and 117 μmol mL1 against CEM compared to melphalan 3.2 μmol mL1 and 2.5 μmol mL1, respectively. The IC50 for compound 7i against L1210 was 7.2 μmol mL1 compared to melphalan 2.1 μmol mL1.Reakcijom 1,5-disupstituiranih 2,3-diokso-2,3-dihidroindola s ortofenilen diaminom sintetizirani su različiti 6-aralkil-9-supstituirani-6H-indolo[2,3-b]kinoksalini. Spojevi 5b, 5d, 5g i 5l pokazali su značajno antitumorsko djelovanje na 59 humanih tumorskih stanica. Svi sintetizirani spojevi ispitani su na citostatsko djelovanje na stanične linije Molt 4/C8 i CEM T-limfocite, te na murin L1210 stanice leukemije. IC50 za spoj 5h je 71 μmol mL1 na staničnu liniju Molt 4/C8 i 117 μmol mL1 na CEM, dok su vrijednosti za melfalan 3,2, odnosno 2,5 μmol mL1. IC50 spoja 7i na stanice L1210 je 7,2 μmol mL1, dok je za melfalan 2,1 μmol mL1

Synthesis and cytostatic evaluation of some 2-(5-substituted-2-oxoindolin-3-ylidene)-N-substituted hydrazine carbothioamide

Various substituted 2-(5-substituted-2-oxoindolin-3-ylidene)-N-substituted hydrazine carbothioamide 4a–g and 2-(5-substituted-1-(4-substituted benzyl)-2-oxoindolin-3-ylidene)-N-substituted hydrazine carbothioamide 5a–k were synthesized. The compounds were evaluated for their cytostatic activity against human Molt4/C8 and CEM T-lymphocytes as well as murine L1210 leukemia cells. Several of these compounds were endowed with low micromolar 50%-inhibitory concentration (IC50) values, and some were virtually equally potent as melphalan. The most potent inhibitors against the murine leukemia cells were also most inhibitory against human T-lymphocyte tumor cells. 2-(5-fluoro-1-(4-fluorobenzyl)-2-oxoindolin-3-ylidene)-N-p-tolylhydrazine carbothioamide (5b) emerged as the most potent cytostatic compound among the tested compounds. The encouraging cytostatic data provide an adequate rationale for further modification of these molecular scaffolds.status: publishe

ST09, A Novel Curcumin Derivative, Blocks Cell Migration by Inhibiting Matrix Metalloproteases in Breast Cancer Cells and Inhibits Tumor Progression in EAC Mouse Tumor Models

Purpose: Curcumin is known for its anticancer and migrastatic activity in various cancers, including breast cancer. Newer curcumin derivatives are being explored to overcome limitations of curcumin like low bioavailability, stability, and side effects due to its higher dose. In this study, the synthesis of ST09, a novel curcumin derivative, and its antiproliferative, cytotoxic, and migrastatic properties have been explored both in vitro and in vivo. Methods: After ST09 synthesis, anticancer activity was studied by performing standard cytotoxicity assays namely, lactate dehydrogenase (LDH) release assay, 3-(4, 5-dimethylthiazol-2-yl)-2-5-diphenyletrazolium bromide (MTT), and trypan blue exclusion assay. Annexin-FITC, cell cycle analysis using flow cytometry, and Western blotting were performed to elucidate cell death mechanisms. The effect on the inhibition of cell migration was studied by transwell migration assay. An EAC (Ehrlich Ascites carcinoma) induced mouse tumor model was used to study the effect of ST09 on tumor regression. Drug toxicity was measured using aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and flow-cytometry based lymphocyte count. Histological analysis was performed for assessment of any tissue injury post ST09 treatment. Results: ST09 shows an approximate 100-fold higher potency than curcumin, its parent compound, on breast tumor cell lines MCF-7 and MDA-MB231. ST09 arrests the cell cycle in a cell type-specific manner and induces an intrinsic apoptotic pathway both in vitro and in vivo. ST09 inhibits migration by downregulating matrix metalloprotease 1,2 (MMP1,2) and Vimentin. In vivo, ST09 administration led to decreased tumor volume in a mouse allograft model by boosting immunity with no significant drug toxicity. Conclusion: ST09 exhibits antiproliferative and cytotoxic activity at nanomolar concentrations. It induces cell death by activation of the intrinsic pathway of apoptosis both in vitro and in vivo. It also inhibits migration and invasion. This study provides evidence that ST09 can potentially be developed as a novel antitumor drug candidate for highly metastatic and aggressive breast cancer

Interstitial brachytherapy for internal mammary node in breast cancer: A case report

This case study reports the feasibility, safety, and efficacy of interstitial brachytherapy for internal mammary nodal recurrence in a 68-year-old woman with triple-negative breast cancer. The patient had previously undergone mastectomy followed by chemotherapy and radiotherapy. However, an internal mammary node was discovered during a routine follow-up a year later, which was confirmed as metastatic carcinoma by fine needle aspiration, with no other metastatic lesions. The patient underwent interstitial brachytherapy under ultrasound and computed tomography (CT) guidance, with a prescribed dose of 20 Gray in one fraction. Follow-up CT scan imaging over a 2-year period of treatment showed a complete resolution of internal mammary node. Therefore, brachytherapy may be considered a potential treatment option for cases of isolated internal mammary node recurrence in breast cancer

Synthesis, antineoplastic and cytotoxic activities of some mononuclear Ru(II) complexes

A series of mononuclear Ru(II) complexes of the type [Ru(S)(2)(K)](2+), where S = 1,10-phenanthroline/2,2'-bipyridine and K = 4-OH-btsz, 4-CH(3)-btsz, 3,4-di-OCH(3)-btsz, 4-OH-binh, 4-CH(3)-binh, 3,4-di-OCH(3)-binh, were prepared and characterized by elemental analysis, FTIR, (1)H-NMR, and mass spectroscopy. The complexes displayed metal-ligand charge transfer (MLCT) transitions in the visible region. These ligands formed bidentate octahedral ruthenium complexes. The title complexes were evaluated for their in vivo anticancer activity against a transplantable murine tumor cell line, Ehrlisch's ascites carcinoma (EAC), and in vitro cytotoxic activity against human cancer cell lines Molt 4/C(8) and CEM and murine tumor cell line L1210. The ruthenium complexes showed promising biological activity especially in decreasing tumor volume and viable ascites cell counts. Treatment with these complexes prolonged the life span of mice bearing EAC tumors by 10-52%. In vitro evaluation of these ruthenium complexes revealed cytotoxic activity from 0.21 to 24 muM against Molt 4/C(8), 0.16 to 19 muM aginst CEM, and 0.75 to 32 muM against L1210.status: publishe

Synthesis and biological evaluation of 2-(5-substituted-1-((diethylamino)methyl)-2-oxoindolin-3-ylidene)-N-substituted-hydrazinecarbothioamides

Abstract: Various 5-substituted-2-(1-((diethylamino)methyl)-2-oxoindolin-3-ylidene)hydrazinecarbothioamide (4a, b) and 5-substituted-2-(1-((diethylamino)methyl)-2-oxoindolin-3-ylidene)-N-(phenyl-4-substituted)hydrazinecarbothioamide (5a-h) derivatives were synthesized. The compounds were screened for cytotoxicity against human HeLa and CEM T-lymphocytes as well as murine L1210 cells. The compounds were also screened for β-lactamase inhibitory activity, antiviral, antibacterial, and antifungal activity against various strains of microorganisms. Several of these compounds were endowed with low micromolar 50 %-cytostatic concentration (IC50) values, and some were virtually equally potent as melphalan. The most potent inhibitors against the murine leukemia cells (L1210) were also the most inhibitory against human T-lymphocyte (CEM) tumor cells. Derivative 2-(1-((diethylamino)methyl)-2-oxoindolin-3-ylidene)-N-(4-methoxyphenyl)hydrazinecarbothioamide 5c emerged as the most potent cytostatic compound among the tested compounds. Derivatives 4b, 5a, 5b, and 5d showed antiviral activity against HEL cell cultures (IC50 11-20 μM). Moderate antimicrobial activity was observed for all derivatives. The encouraging cytostatic and antiviral activity data provide an adequate rationale for further modification of these molecular scaffolds. Graphical abstract: Derivative 5c (1.9-4.4 μM) emerged as the most potent cytostatic compound among the tested compounds. Derivatives 4b, 5a, 5b, and 5d showed antiviral activity against HEL cell cultures (IC50 11-20 μM).status: publishe

A Novel Resveratrol Based Tubulin Inhibitor Induces Mitotic Arrest and Activates Apoptosis in Cancer Cells

Resveratrol is one of the most widely studied bioactive plant polyphenols which possesses anticancer properties. Previously we have reported synthesis, characterization and identification of a novel resveratrol analog, SS28. In the present study, we show that SS28 induced cytotoxicity in several cancer cell lines ex vivo with an IC50 value of 3-5 mu M. Mechanistic evaluation of effect of SS28 in non-small cell lung cancer cell line (A549) and T-cell leukemic cell line (CEM) showed that it inhibited Tubulin polymerization during cell division to cause cell cycle arrest at G2/M phase of the cell cycle at 12-18 h time period. Immunofluorescence studies confirmed the mitotic arrest upon treatment with SS28. Besides, we show that SS28 binds to Tubulin with a dissociation constant of 0.414 +/- 0.11 mu M. Further, SS28 treatment resulted in loss of mitochondrial membrane potential, activation of Caspase 9 and Caspase 3, leading to PARP-1 cleavage and finally cell death via intrinsic pathway of apoptosis. Importantly, treatment with SS28 resulted in regression of tumor in mice. Hence, our study reveals the antiproliferative activity of SS28 by disrupting microtubule dynamics by binding to its cellular target Tubulin and its potential to be developed as an anticancer molecule