Synthesis and in vitro antiproliferative and antibacterial activity of new thiazolidine-2,4-dione derivatives

In our present research, we synthesised new thiazolidine-2,4-diones (12–28). All the newly synthesised compounds were evaluated for antiproliferative and antibacterial activity. Antiproliferative evaluation was carried out using normal human skin fibroblasts and tumour cell lines: A549, HepG2, and MCF-7. The IC₅₀ values were determined for tested compounds revealing antiproliferative activity. Moreover, safety index (SI) was calculated. Among all tested derivatives, the compound 18 revealed the highest antiproliferative activity against human lung, breast, and liver cancer cells. More importantly, the derivative 18 showed meaningfully lower IC₅₀ values when compared to the reference substance, irinotecan, and relatively high SI values. Moreover, newly synthesised compounds were screened for the bacteria growth inhibition in vitro. According to our screening results, most active compound was the derivative 18 against Gram-positive bacteria. Therefore, it may be implied that the novel compound 18 appears to be a very promising agent for anticancer treatment.     

Synthesis and antimicrobial activity of some new thiazolyl thiazolidine-2,4-dione derivatives

In this study, a series of thiazolyl thiazolidine-2,4-dione derivatives (Va-f and VIa-f) were synthesized and evaluated for their antibacterial and antifungal activities against Staphylococcus aureus (ATCC 25923), methicillin resistant S. aureus (MRSA ATCC 43300), methicillin resistant S. aureus (MRSA isolate), and Escherichia coli (ATCC 23556) and C. albicans (ATCC10145). All the compounds were found active against used microorganisms.     

Synthesis and antiproliferative activity of some novel derivatives of diospyrin, a plant-derived naphthoquinonoid

Derivatisation of diospyrin, a bisnaphthoquinonoid isolated from Diospyros montana Roxb., led to the modification of its inhibitory activity, in vitro, towards a murine tumour model, Ehrlich ascites carcinoma (EAC), and two human cancer cell lines, viz., malignant skin melanoma (A375) and epidermoid laryngeal carcinoma (Hep2). Among the novel derivatives, an epoxide exhibited the maximum antiproliferative activity (IC(50) values in the range of 0.03-0.21 microM) and a comparatively lower toxicity (IC(50) approximately 98 microM) in normal human peripheral blood mononuclear cells (PBMC). This compound might provide a novel 'lead' for the development of clinically effective antiproliferative agents against cancer.     

Synthesis and antiproliferative activity of new cytotoxic tri- and tetraazabenzo[3,2-a]fluorene-5,6-dione derivatives

A new series of substituted tri-/tetraazabenzo[3,2-a]fluorene-5,6-diones and their corresponding oxime derivatives have been synthesized and spectroscopically characterized. The antiproliferative activities of all compounds were evaluated on at least three different cell lines.     

Synthesis and antiproliferative activity of some steroidal lactams

Using cholesterol as starting material, a series of 6-substituted-3-aza-A-homo-3-oxycholestanes and 6-substituted-4-aza-A-homo-3-oxycholestanes were synthesized by the oxidation, reduction, oximation, Beckman rearrangement and condensation reaction. These synthesized compounds displayed a distinct cytotoxicity against MGC 7901, HeLa and SMMC 7404 cancer cells. Our results revealed that the structures of functional groups at position-6 on the steroidal ring are crucial for the IC₅₀ value of antiproliferative activities of these compounds and the cytotoxic activity against MGC 7901 and SMMC 7404 cells was not significantly different between 4-N-lactams and 3-N-lactams when its 6-substituted group was a carbonyl or a hydroximino, but all 3-N-lactams showed a higher cytotoxicity against HeLa cells than 4-N-lactams. In particular, compounds 6, 8, 9 (IC₅₀6: 6.5 μmol/L; 8: 7.7 μmol/L; 9: 5.6 μmol/L) were even more cytotoxic than cisplatin to HeLa cells (positive contrast, 10.1 μmol/L). The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.     

Synthesis and antiproliferative activity of some diaryldiazepines and diarylpyrimidines

Novel substituted 5,7-diaryl-2,3-dihydro-1,4-diazepines and 4,6-diaryl-2-aminopyrimidines were synthesized and tested for their antiproliferative activity. Title compounds were obtained by cyclocondensation of a substituted flavone with ethylenediamine and guanidine respectively. The cytotoxicity in vitro against various human leukemic cancer cell lines viz., Jurkat, HL60, MOLT3, NCEB-1, K562 was determined.     

Synthesis and antiproliferative activity of some diaryldiazepines and diarylpyrimidines

Novel substituted 5,7-diaryl-2,3-dihydro-1,4-diazepines and 4,6-diaryl-2-aminopyrimidines were synthesized and tested for their antiproliferative activity. Title compounds were obtained by cyclocondensation of a substituted flavone with ethylenediamine and guanidine respectively. The cytotoxicity in vitro against various human leukemic cancer cell lines viz., Jurkat, HL60, MOLT3, NCEB-1, K562 was determined.     

Synthesis and antiviral/antiproliferative activity of some N-sulphonylbenzimidazoles

Some benzimidazolyl sulphones were synthesized and evaluated for their antiviral and antiproliferative properties. Compound 10 displayed significant and selective activity against human cytomegalovirus (CMV), compound 14 showed activity against varicella zoster virus (VZV). The compounds were further evaluated for inhibitory effect on the proliferation of murine leukemia cells and human T-lymphocyte cells. Marked cytotoxicity was noted with different derivatives. Some structure-activity relationships are discussed.     

Synthesis and antiproliferative activity of some steroidal lactone compounds

Using cholesterol as starting material, some steroidal lactone compounds with the structures of 3-substituted-6-oxo-7-oxa-B-homo-cholestane or 3-substituted-7-oxo-6-oxa-B-homo-cholestane were synthesized by oxidation, reduction, Baeyer-Villiger reaction and condensation reaction. The cytotoxicity of these compounds against MGC 7901 (human gastric carcinoma), HeLa (human cervical carcinoma) and SMMC 7404 (human liver carcinoma) cells was investigated. Our results showed that the synthesized compounds displayed a distinct cytotoxicity against these cancer cells. In particular, compounds 8 and 9 have similar cytotoxic capability as cisplatin does. The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.     

Synthesis,antiproliferative activity and molecular docking of Colchicine derivatives

In order to create more potent anticancer agents, a series of five structurally different derivatives of Colchicine have been synthesised. These compounds were characterised spectroscopically and structurally and their antiproliferative activity against four human tumour cell lines (HL-60, HL-60/vinc, LoVo, LoVo/DX) was evaluated. Additionally the activity of the studied compounds was calculated using computational methods involving molecular docking of the Colchicine derivatives to β-tubulin. The experimental and computational results are in very good agreement indicating that the antimitotic activity of Colchicine derivatives can be readily predicted using computational modeling methods.     

Synthesis and antiproliferative activity of some new DNA-targeted alkylating pyrroloquinolines

Two novel DNA-direct alkylating agents, consisting of aniline mustard linked to an angular 3H-pyrrolo[3,2-f]quinoline nucleus, were synthetized and assayed for their in vitro antiproliferative activity. Simple convergent synthesis, consisting of separate preparation of 9-chloro-3H-pyrrolo[3,2-f]quinoline and p-amino-aniline derivatives, and following their linkage by substitution reactions 8a, b and 10, yielded the corresponding diol derivatives 7b and 9. Biological properties were evaluated with respect to cell growth inhibition, ability to form cross-links with DNA, and capacity to give rise to a molecular complex with the macromolecule for 7b, 8b, 9 and 10.     

Synthesis and antiproliferative activity of C-homo-lactam derivatives of 7-deoxycholic acid

Using deoxycholic acid as starting materials, a series of 12a-aza-C-homo-12-one 7-deoxycholic acid derivatives were synthesized The antiproliferative activity of the synthesized compounds against some carcinoma cell lines was investigated. The results showed that some 12-oxy-12a-aza-C-homo-7-deoxycholic acid derivatives displayed distinct cytotoxicity to HeLa (human cervical carcinoma) and Tu 686 (laryngocarcinoma) tumor cell lines. In particular, the IC₅₀ values of the compounds 6 and 7 against Tu 686 cells are 16.7 and 19.8 μM/L respectively. The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.     

Synthesis and characterization of novel 1,2,4-triazine derivatives with antiproliferative activity

A series of novel small molecules with a 1,2,4-triazine scaffold was obtained according to a recently published and highly efficient synthetic route. Screening for antiproliferative and cytotoxic activity revealed distinct anticancer effects against the human leukemia cell line K-562 combined with a remarkable low cytotoxicity. All compounds were in agreement with the ‘rule-of-five’ claims by Lipinski and calculated log P_calc values were experimentally confirmed (log P_exp). For the most active compounds, in vitro serum albumin binding was investigated and structure–activity relationships were established.     

Synthesis and activity evaluation of benzoylurea derivatives as potential antiproliferative agents

3-Haloacylamino benzoylureas (3-HBUs) consist of a new family of tubulin ligands that kill cancer cells through mitotic arrest. In exploring the structure–activity relationship (SAR), 17 analogues defined through variations of formylurea at the 1-position of the aromatic ring were synthesized. SAR analysis revealed that (i) the p–π conjugation between the aromatic ring and formylurea was essential; (ii) suitable aryl substitutions at the N′-end increased anticancer activity with a mechanism different from that of parent compounds; and (iii) introduction of pyridyl at the N′-end provided an opportunity of making soluble salts to improve bioavailability. Among the analogues, 16c bearing 3,4,5-trimethoxyphenyl and 16g bearing 2-pyridyl at the N′-end showed an enhanced activity and were active in hepatoma cells that were resistant to tubulin ligands including the parent compounds. Furthermore, 16c and 16g killed cancer cells with a mechanism independent of mitotic arrest, indicating a change of action mode.     

Synthesis and structure-antituberculosis activity relationship of 1H-indole-2,3-dione derivatives

New series of 5-fluoro-1H-indole-2,3-dione-3-thiosemicarbazones 2a-k and 5-fluoro-1-morpholino/piperidinomethyl-1H-indole-2,3-dione-3-thiosemicarbazones 3a-r were synthesized. The structures of the synthesized compounds were confirmed by spectral data, elemental and single crystal X-ray diffraction analysis. The new 5-fluoro-1H-indole-2,3-dione derivatives, along with previously reported 5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones 2l-v, 1-morpholino/piperidinomethyl-5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones 4a-l, and 5-nitro-1H-indole-2,3-dione-3-[(4-oxo-1,3-thiazolidin-2-ylidene)hydrazones] 5a-s, were evaluated for in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv. Among the tested compounds, 5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones (2p, 2r, and 2s) and its 1-morpholinomethyl derivatives (4a, 4e, 4g, and 4i) exhibited significant inhibitory activity in the primary screen. The antituberculosis activity of molecules with diverse skeletons was investigated by means of the Electronic-Topological Method (ETM). Ten pharmacophores and ten anti-pharmacophores that have been found by this form the basis of the system capable of predicting the structures of potentially active compounds. The forecasting ability of the system has been tested on structures that differ from those synthesized. The probability of correct identification for active compounds was found as equal to 93% in average. To obtain the algorithmic base for the activity prediction, Artificial Neural Networks were used after the ETM (the so-called combined ETM-ANN method). As the result, only 9 pharmacophores and anti-pharmacophores were chosen as the most important ones for the activity. By this, ANNs classified correctly 94.4%, or 67 compounds from 71.     

Synthesis,inhibition of NO production and antiproliferative activities of some indole derivatives

The synthesis and the biological evaluation of pyrano[3,2-e]indoles and their reaction intermediates are described. The compounds prepared were evaluated for their inhibition of NO production, antioxidant activity and also for their ability to inhibit in vitro the growth of four human tumor cell lines: large lung carcinoma (COR-L23), alveolar basal epithelial carcinoma (A549), amelanotic melanoma (C32) and melanoma (A375). The two reaction intermediates, 5a and 5b, showed the highest inhibition of NO production in murine monocytic macrophage (IC₅₀?=?1.1?μM and IC₅₀?=?2.3 μM respectively). Compound 5a was the most active against melanotic melanoma (IC₅₀?=?11.8?μM) while the other compounds exhibited weak cytotoxicity with IC₅₀ values >50?μM on all cell lines.     

Synthesis and analgesic activity of some acetamide derivatives

In the present study, some acetamide derivatives were synthesized and their potential analgesic activities were investigated. N-(benzothiazol-2-yl)-2-[(1-substituted-1H-tetrazol-5-yl)thio]acetamide derivatives were obtained by the nucleophilic substitution reaction of 2-chloro-N-(benzothiazole-2-yl)acetamides with appropriate tetrazol-5-thioles. The chemical structures of the compounds were elucidated by IR, ¹H-NMR, ¹³C-NMR and FAB⁺-MS spectral data and elemental analyses. The prepared compounds were investigated for their potential analgesic properties against thermal, mechanical and chemical nociceptive stimuli using hot-plate, tail-clip and acetic acid-induced writhing tests, respectively. The assessment of motor coordination was carried out using Rota-Rod test. Tested compounds applied at 100?mg/kg doses caused significant decrease in acetic acid-induced writhing responses and increase in hot-plate and tail-clip latencies. None of the compounds exhibited destructive effect on motor coordination of the mice in Rota-Rod performance.     

Synthesis and antiproliferative activity of some steroidal thiosemicarbazones,semicarbazones and hydrozones

Steroidal thiosemicarbazones, semicarbazones and hydrazones have received extensive attention of scientists recently because they exhibit some biological activities such as antibacterial, antiviral and anticancer. Using different steroids as starting materials, through different chemical methods, 24 steroidal compounds with thiosemicarbazone, semicarbazone or hydrazone groups in their structures, were synthesized, characterized by IR, NMR and MS. The antiproliferative activity of the compounds was evaluated against human gastric cancer (SGC-7901) and human liver cancer (Bel-7404) cells. The structure–activity relationship of these compounds was discussed. The results showed that compound 3 and 12a–12c exhibited significant inhibitory activity to Bel-7404 cells, and IC₅₀ values of them were 4.2, 11.0, 7.4 and 15.0 μM respectively (Cisplatin, IC₅₀: 11.6 μM).     

Synthesis and antiproliferative activity of some 4'-C-hydroxymethyl-alpha- and -beta-D-arabino-pentofuranosyl pyrimidine nucleosides

A suitably protected 4-C-hydroxymethyl-arabino-pentofuranose was prepared and condensed with the following nucleobases: uracil, 5-fluorouracil and thymine. The corresponding cytosine and 5-fluorocytosine derivatives have also been obtained respectively from the uracil and 5-fluorouracil nucleosides. Separation of the anomeric mixtures followed by deprotection afforded the target compounds that were found to be non-cytotoxic to CCRF-CEM leukemia cells.     

Synthesis and anticandidal activity of some imidazopyridine derivatives

New hydrazide derivatives of imidazo[1,2-a]pyridine have been synthesized and evaluated for anticandidal activity. The reaction of imidazo[1,2-a]pyridine-2-carboxylic acid hydrazides with various benzaldehydes gave N-(benzylidene)imidazo[1,2-a]pyridine-2-carboxylic acid hydrazide derivatives. Their anticandidal activities against Candida albicans and Candida glabrata (isolates obtained from Osmangazi University, Faculty of Medicine, Eskisehir, Turkey), Candida albicans (ATCC 90028), Candida utilis (NRLL Y-900), Candida tropicalis (NRLL Y-12968), Candida krusei (NRLL Y-7179), Candida zeylanoides (NRLL Y-1774), and Candida parapsilosis (NRLL Y-12696) were investigated.