Syntheses of heterocyclic derivatives as potential cytotoxic compounds evaluated toward hepatocellular and cervical carcinoma cell lines

ABSTRACT. Through the present work the 3-oxo-N,3-diphenylpropamide derivatives 5a,b were used to synthesize pridine, pyrazole and thiophene derivatives. 3-Phenylisoxazol-5(4H)-one produced from the reaction of ethyl benzoylacetate was used as the key starting compound for different multi-component reactions. The synthesized compounds were evaluated toward Hepatocellular carcinoma HepG2 and cervical carcinoma HeLa cell lines. Compounds 3b, 5b, 7b, 7d, 9c, 9d, 15e, 15f, 16b, 18b, 18e, 18f, 19e and 19f were the most cytotoxic compounds against the tested cell lines. The results obtained in this work encourage further work in the future to produce new cytotoxic compounds.   KEY WORDS: Diphenylpropamide, 3-Phenylisoxazole, Pyran, Pyridine, Cytotoxicity Bull. Chem. Soc. Ethiop. 2023, 37(1), 141-158.                                                              DOI:https://dx.doi.org/10.4314/bcse.v37i1.1

Uses of chalcone acetophenone to synthesis heterocyclic compounds with cytotoxic and c-Met kinase activities

ABSTRACT. The aim of present study was the uses of a series of α,β-unsaturated carbonyl compounds (chalcones), in the synthesis of pyridine, pyran, thiophene, thiazole, together with their uses in heterocyclic synthesis. The work has resulted in the synthesis of a variety of 2,5-dihydropyridine, hydrazide-hydrazone, thiophene derivatives, coumarin, pyran and thiazolo[4,5-d]thiazole derivatives. The antitumor activities of the newly synthesized products were carried out against three cancer cell lines namely MCF-7, NCI-H460 and SF-268 and normal human cell line WI38.  In addition, the inhibitions of most of the synthesized compounds against             c-Met kinase were studied and results showed that many compounds were of high inhibitions, and these are considered as promising anticancer agents. The results obtained encouraged further work in the future.    KEY WORDS: Chalcones, Heterocyclic, Pyridine, Pyran, Thiophene, Thiazole, Antitumor Bull. Chem. Soc. Ethiop. 2022, 36(1), 149-172.                                                             DOI: https://dx.doi.org/10.4314/bcse.v36i1.13                                                      &nbsp

Multi-component reactions of cyclohexan-1,3-dione to synthesize heterocyclic derivatives with c-Met enzymatic activity, anti-prostate, anti-proliferative and tyrosine kinase activities

ABSTRACT. We are aiming in this work to synthesize target molecules not only possess anti-tumor activities but also kinase inhibitors. The target molecules were obtained starting from aryl hydrazones of cyclohexan-1,3-dione  followed by its heterocyclization reactions to produce anticancer molecules. The multi-component reactions of the arylhydrazocyclohexan-1,3-dione derivatives 3a-c produced the 1,4,5,6,7,8-hexahydroquinoline derivatives 6a-r and the 4,5,6,8-tetrahydrochromeno[2,3-c]pyrazole derivatives 10a-c. Other multi-component reactions were demonstrated. The anti-proliferative activity of the synthesized compounds toward the six cancer cell lines namely A549, H460, HT-29, MKN-45, U87MG, and SMMC-7721 was studied. In addition the c-Met enzymatic activities and inhibition toward the prostate cancer cell PC-3 were measured. The results obtained in most cases, indicated that the presence of electronegative Cl group through the molecule favour the inhibitions.                 KEY WORDS: Multi-component reactions, Cyclohexan-1,3-dione, Chromene, Chromeno[2,3-c]pyrazole, Cytotoxicity   Bull. Chem. Soc. Ethiop. 2022, 36(1), 119-136.                                                             DOI: https://dx.doi.org/10.4314/bcse.v36i1.11                                                      &nbsp

Synthesis and cytotoxicity evaluation of thiazole derivatives obtained from 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile

Reactivity of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile towards thioglycolic acid resulted in thiazole derivative 1. The latter reacted with different chemical reagents to give thiazole, pyrano[2,3-d]thiazole and thiazolo[4,5-d]thiazole derivatives. Cytotoxicity effects of the newly synthesized products against six cancer cell lines, namely, human gastric cancer (NUGC), human colon cancer (DLD-1), human liver cancer (HA22T and HEPG-2), human breast cancer (MCF) and nasopharyngeal carcinoma (HONE-1) as well as against a normal fibroblast cell (WI-38) were evaluated. The study showed that the 4,5,6,7 tetrahydrobenzo[b]thiophene derivatives 6a, 7, 8a,b, 9b and 10b,c were the most active compounds. Their potencies were attributed to the presence of the electron withdrawing groups

Antiproliferative and Antiprostate Cancer Activities of Heterocyclic Compounds Derived from Cyclohexane-1,4-dione

2-Amino-6-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (3) was prepared from the reaction of cyclohexane-1,4-dione with elemental sulfur and malononitrile in 1,4-dioxane and triethylamine as catalyst. The latter compound reacted with triethyl orthoformate and either malononitrile or ethyl cyanoacetate in 1,4-dioxane in the presence of triethylamine to produce 4H-thieno[2,3-f]chromene derivatives 10a,b. In addition, fused pyran and pyridine derivatives were synthesized starting from compound 3. The cytotoxicity of the synthesized compounds was studied on six cancer cell lines together with c-Met kinase and PC-3 cell line. The most active compounds were tested against five tyrosine kinases and Pim-1 kinase, most of which showed strong inhibition, encouraging further work

Heterociklički derivati progesterona s antimikrobnim djelovanjem

The aim of this work was to synthesize steroidal heterocycles and to elucidate the potential role of these compounds as antimicrobial agents. The synthesis of steroidal heterocycles containing the pyrazole, isoxazole, thiazole, pyrane, pyridine, pyridazine, or benzopyrane ring attached to the pregnene nucleus is reported. Progesterone (1) reacts with dimethyl formamide dimethyl acetal to form enamine 2. Heterocyclization of 2 with hydrazines, hydroxylamine, glycine, ethylacetoacetate or cyanomethylene afforded novel steroidal heterocyclic derivatives. The in vitro antimicrobial evaluation showed that all synthesized compounds show activity against the used strains of Gram positive bacteria and fungi.U radu je opisana sinteza steroidnih heterocikličkih spojeva i evaluacija njihovog antimikrobnog djelovanja. Sintetizirani spojevi sadrže pirazol, izoksazol, tiazol, piran, piridin, piridazin ili benzopiran na pregnenskoj jezgri. Progesteron (1) je prvo u reakciji s dimetil formamid dimetil acetalom dao enamin 2. Novi steroidni heterociklički derivati dobiveni su heterociklizacijom spoja 2 s hidrazinima, hidroksilaminom, glicinom, etilacetoaceatom i cijanometilenom. Antimikrobno vrednovanje in vitro pokazalo je da su svi sintetizirani spojevi aktivni protiv testiranih Gram pozitivnih bakterija i gljivica

Reakcija β-amino-α,γ-dicianokrotononitrila s acetofenonom: sinteza derivata piridina, piridazina i tiofena s antimikrobnim djelovanjem

Condensation of β-amino-α,γ-dicyanocrotononitrile (1) with acetophenone gave the 2-amino-4-phenylpenta-1,3-diene-1,1,3-tricarbonitrile (2). The latter product was used in a series of heterocyclization reactions when react with different reagents like diazonium salts, hydrazines, hydroxylamine and elemental sulfur to give pyridazine, pyrazole, isoxazole and thiophene derivatives, respectively. On the other hand, it gave pyridine derivatives with aromatic aldehydes followed by reaction with cyanomethylene reagents. The MIC values for the newly synthesized product were measured against E. coli, B. cereus, B. subtilis and C. albicansKondenzacijom β-amino-α,γ-dicijanokrotononitrila 1 s acetofenonom dobiven je 2-amino-4-fenilpenta-1,3-dien-1,1,3-trikarbonitril (2) koji je upotrebljen u reakcijama heterociklizacije s različitim reagensima poput diazonijevih soli, hidrazina, hidroksilamina i elementarnog sumpora pri čemu su nastali derivati piridazina, pirazola, izoksazola, odnosno tiofena. Spoj 2 je u reakciji s aromatskim aldehidima te naknadno sa cijanometilenima dao derivate piridina. Određene su MIC vrijednosti za novosintetizirane spojeve protiv E. coli, B. cereus, B. subtilis i C. albicans

Novel Synthesis of Hydrazide-Hydrazone Derivatives and Their Utilization in the Synthesis of Coumarin, Pyridine, Thiazole and Thiophene Derivatives with Antitumor Activity

The reaction of cyanoacetyl hydrazine (1) with 3-acetylpyridine (2) gave the hydrazide-hydrazone derivative 3. The latter compound undergoes a series of heterocyclization reactions to give new heterocyclic compounds. The antitumor evaluation of the newly synthesized products against three cancer cell lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) was performed. Most of the synthesized compounds showed high inhibitory effects

Uses of 3-(2-Bromoacetyl)-2H-chromen-2-one in the Synthesis of Heterocyclic Compounds Incorporating Coumarin: Synthesis, Characterization and Cytotoxicity

In this work, 3-bromoacetylcoumarin was used as the key starting material for the synthesis of pyran, pyridine, thiophene, thiazole and pyrazole derivatives through its reaction with different reagents. The structures of the newly synthesized compounds were confirmed on the basis of their spectral data and elemental analyses. All of the synthesized compounds were screened for their in vitro anticancer activity against six human cancer cell lines, namely: human gastric cancer (NUGC), human colon cancer (DLD1), human liver cancer (HA22T and HEPG2), nasopharyngeal carcinoma (HONE1), human breast cancer (MCF) and normal fibroblast cells (WI38). The IC50 values (the sample concentration that produces 50% reduction in cell growth) in nanomolars (nM)) showed most of the compounds exhibited significant cytotoxic effect. Among these derivatives, compound 6d showed almost equipotent cytotoxic activity against NUGC (IC50 = 29 nM) compared to the standard CHS 828 (IC50 = 25 nM)