K. Vinaya

Synthesis of 2-(5-((5-(4-chlorophenyl)furan-2-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)acetic acid derivatives and evaluation of their cytotoxicity and induction of apoptosis in human leukemia cells.

In order to explore the anticancer effect associated with the thiazolidinone framework, several 2-(5-((5-(4-chlorophenyl)furan-2-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)acetic acid derivatives 5(a-l) were synthesized. Variation in the functional group at C-terminal of the thiazolidinone led to set of compounds bearing amide moiety. Their chemical structures were confirmed by (1)H NMR, IR and Mass Spectra analysis. These thiazolidinone compounds containing furan moiety exhibits moderate to strong antiproliferative activity in a cell cycle stage-dependent and dose dependent manner in two different human leukemia cell lines. The importance of the electron donating groups on thiazolidinone moiety was confirmed by MTT and Trypan blue assays and it was concluded that the 4th position of the substituted aryl ring plays a dominant role for its anticancer property. Among the synthesized compounds, 5e and 5f have shown potent anticancer activity on both the cell lines tested. To rationalize the role of electron donating group in the induction of cytotoxicity we have chosen two molecules (5e and 5k) having different electron donating group at different positions. LDH assay, Flow cytometric analysis and DNA fragmentation suggest that 5e is more cytotoxic and able to induce the apoptosis.

Synthesis and in vitro antiproliferative activity against human cancer cell lines of novel 5-(4-methyl-benzylidene)-thiazolidine-2,4-diones

SummaryA series of novel 5-(4-methyl-benzylidene)-thiazolidine-2,4-dione derivatives 6 (a–d) and 7 (a–g) were synthesized with different substituted aromatic sulfonyl chlorides (R–SO2–Cl) and alkyl halides (R–X) and were characterized by 1H NMR, LC/MS, FTIR and elemental analyses. All the compounds synthesised were evaluated for their cell antiproliferation activity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The antiproliferative effects of the synthesised compounds were tested against viable human skin fibroblast cell line and carcinoma cell lines namely HeLa cells, HT-29 cells, MCF-7 cells, HepG-2 cells by adopting positive and negative control. The importance of the nitro group on thiazolidinone moiety was confirmed and it was concluded that the fourth position of the substituted aryl ring plays a dominant role and was responsible for the antiproliferative activity. Among the synthesized compounds only 6a, 7e and 7g have potent antiproliferative activity on all the carcinoma cell lines tested.

Synthesis and in vitro antiproliferative activity of novel 1-benzhydrylpiperazine derivatives against human cancer cell lines

In order to explore the antiproliferative effect associated with the piperazine framework, several 1-benzhydrylpiperazine derivatives 8(a-d), 9(a-d) and 10(a-h) were synthesized. Variation in the functional group at N-terminal of the piperazine led to three sets of compounds, bearing the sulfonyl, amide and thiourea, respectively. Their chemical structures were confirmed by (1)H NMR, LCMS, IR and elemental analysis. The antiproliferative effect of the compounds were evaluated in vitro using the MTT colorimetric method against one normal cell line (NF-103 skin fibroblast cells) and four human cancer cell lines (MCF-7 breast carcinoma cell line, HepG-2 hepatocellular carcinoma cell line, HeLa cervix carcinoma cell line and HT-29 colon carcinoma cell line) for the time period of 24 h. Among the series, four compounds exhibited interesting growth inhibitory effects against all four cell lines.

Synthesis and in vivo anticancer and antiangiogenic effects of novel thioxothiazolidin-4-one derivatives against transplantable mouse tumor

A series of novel thioxothiazolidin-4-one derivatives 5(a–g) were synthesized by the coupling of different amines containing aliphatic, substituted aromatic, and heterocyclic moieties, such as oxadiazol, pyrazole, isoxazole, and piperazine with 2-(5-(4-chlorophenyl)furan-2-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)acetic acid. All compounds were characterized by 1H NMR, LCMS, FTIR and elemental analysis. In this study, we investigated the possibility that these novel thioxothiazolidin-4-one derivatives 5(a–g) inhibits tumor growth and tumor induced angiogenesis using mouse Ehrlich Ascites Tumor (EAT) as a model system. Our results demonstrated that the compounds significantly reduced ascites tumor volume, cell number, and increased the life span of EAT-bearing mice. In addition, the compounds manifested strong antiangiogenic effects and suppressed tumor induced endothelial proliferation in the mice peritoneum. From our findings, it is noted that the derivatives 5(a–e) may be possible candidates for anticancer therapy with the ability to inhibit tumor angiogenesis and tumor cell proliferation.

Synthesis and antimicrobial studies of novel 1-benzhydryl-piperazine sulfonamide and carboxamide derivatives

A series of novel substituted 1-benzhydryl-piperazine sulfonamide 8(a–f) and benzamides 9(a–h) were synthesized and their antimicrobial activities evaluated in vitro by paper disc diffusion and micro dilution method against standard strains of Gram-positive (Staphylococcus aureus ATCC 25953, Staphylococcus epidermis 25212, Bacillus cereus 11778, Bacillus substilis 6051) and Gram-negative (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 2853, Proteus vulgaris ATCC 2853 and Salmonella typhi ATCC 9484) bacteria. Among the synthesized new compounds 8d, 8e, 9c, 9e, 9f and 9 h showed potent antimicrobial activities compared to the standard drug streptomycin.

Synthesis and Antileukemic Activity of Novel 4-(3-(Piperidin-4-yl) Propyl)Piperidine Derivatives

To explore the anticancer effect associated with the piperidine framework, several (substituted phenyl) {4‐[3‐(piperidin‐4‐yl)propyl]piperidin‐1‐yl} methanone derivatives 3(a–i) were synthesized. Variation in the functional group at N‐terminal of the piperidine led to a set of compounds bearing amide moiety. Their chemical structures were confirmed by 1H NMR, IR and mass spectra analysis. Among these, compounds 3a, 3d and 3e were endowed with antiproliferative activity. The most active compound among this series was 3a with nitro and fluoro substitution on the phenyl ring of aryl carboxamide moiety, which inhibited the growth of human leukemia cells (K562 and Reh) at low concentration. Comparison with other derivative (3h) results shown by LDH assay, cell cycle analysis and DNA fragmentation suggested that 3a is more potent to induce apoptosis.

Synthesis and identification of a new class of antileukemic agents containing 2-(arylcarboxamide)-(S)-6-amino-4,5,6,7-tetrahydrobenzo[d]thiazole.

Recently we have reported the effect of (S)-6-aryl urea/thiourea substituted-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazole derivatives as potent anti-leukemic agents. To elucidate further the Structure Activity Relationship (SAR) studies on the anti-leukemic activity of (S)-2,6-diamino-4,5,6,7-tetrahydrobenzo[d]thiazole moiety, a series of 2-arlycarboxamide substituted-(S)-6-amino-4,5,6,7-tetrahydrobenzo[d]thiazole were designed, synthesized and evaluated for their anti-leukemic activity by trypan blue exclusion, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) assays and cell cycle analysis. Results suggest that the position, number and bulkiness of the substituent on the phenyl ring of aryl carboxamide moiety at 2nd position of 6-amino-4,5,6,7-tetrhydrobenzo[d]thiazole play a key role in inhibiting the proliferation of leukemia cells. Compounds with ortho substitution showed poor activity and with meta and para substitution showed good activity.

Synthesis and cytotoxic evaluation of novel 2-(4-(2,2,2-trifluoroethoxy)-3-methylpyridin-2-ylthio)-1H-benzo[d]imidazole derivatives

The present work deals with the anticancer effect of benzimidazole derivatives associated with the pyridine framework. By varying the functional group at N-terminal of the benzimidazole by different L-amino acids, several 2-(4-(2,2,2-trifluoroethoxy)-3-methylpyridin-2-ylthio)-1Hbenzo[d]imidazole derivatives 9(a–j) were synthesized. Their chemical structures were confirmed by 1H NMR, IR and mass spectroscopic techniques. The synthesized compounds were examined for their antiproliferative effects against human leukemia cell lines, K562 and CEM. The preliminary results showed most of the derivatives had moderate antitumor activity. Compound 9j containing cysteine residue exhibited good inhibition compared to other amino acid resides. In addition DNA fragmentation results suggest that 9j is more cytotoxic and able to induce apoptosis.

Evaluation of in vivo wound-healing potential of 2-[4-(2,4-dimethoxy-benzoyl)-phenoxy]-1-[4-(3-piperidin-4-yl-propyl)-piperidin-1-yl]-ethanone derivatives

Series of 2-[4-(2,4-dimethoxy-benzoyl)-phenoxy]-1-[4-(3-piperidin-4-yl-propyl)-piperidin-1-yl]-ethanone derivatives 9(a-d) and 10(a-d) were synthesized in good yield. The synthesized compounds were characterized by (1)H NMR, LC-MS, FTIR and elemental analysis. All the compounds were screened for in vivo wound-healing activity by incision and dead space wound models on Swiss albino rats. Significant wound healing was observed in 10b and 10d treated groups as also the epithelialization of the incision wound was faster with a high rate of wound contraction in these groups. The tensile strength of the incision wound was significantly increased in 10b and 10d compared to the Nitrofurazone, the standard skin ointment. In dead space wound model also the weight of the granulation was higher indicating increase in collagenation. The SAR correlation studies revealed that the thioamide functional linkage and electron withdrawing groups influence the wound-healing activity.

Synthesis and in vitro antiproliferative activity of diphenyl(sulphonylpiperidin-4-yl)methanol derivatives

A series of novel diphenyl(piperidin-4-yl)methanol derivatives 10(a–n) were synthesized and characterized by 1H NMR, LC/MS, FTIR, and elemental analyses. All the synthesized compounds were evaluated for cell proliferation by MTT assay. The antiproliferative effects of the synthesized compounds were tested against viable human skin fibroblast cell line and carcinoma cell lines, namely HeLa cells, HT-29 cells, MCF-7 cells, and HepG-2 cells in comparing the positive and negative control. Among the synthesized compounds, (10b) and (10g) have been identified as potent antiproliferative agents.