HL-60 Cancer Cell Lines Research Articles

Guaiane-type sesquiterpenes from Curcumawenyujin

Eight undescribed sesquiterpenes including seven guaianes and one pseudoguaiane which were named as wenyujinols A-H, along with ten known guaianes, were isolated from rhizomes of Curcuma wenyujin Y. H. Chen et C. Ling. The structures of wenyujinols A-H were elucidated by 1D and 2D nuclear magnetic resonance (NMR) data, high resolution mass spectrum (HRMS), electronic circular dichroism (ECD) spectra, and X-ray single crystallographic analysis. All of the isolated compounds were evaluated for antioxidant activity via activation of the Nrf2-ARE pathway in human embryonic kidney (HEK) 293 cells, for inhibitory effects on NO production in RAW 264.7 cells, and for cytotoxicity against three human cancer cell lines A549, HL60, and MCF7 in vitro. The results indicated that procurcumenol (50–200 μM) and 9-oxo-neoprocurcumenol (25–200 μM) exhibited antioxidant activity via activation of the Nrf2-ARE pathway in a dose-dependent manner.

Nine new sesquiterpenes from Curcuma wenyujin rhizomes

Nine new sesquiterpenes wenyujinones A-I (1–9), along with ten known ones (10–19), were isolated from the rhizomes of Curcuma wenyujin Y. H. Chen et C. Ling (C. wenyujin). The chemical structures of compounds 1–9 were elucidated by NMR spectroscopic and mass spectrometric data, electronic circular dichroism (ECD) spectra analysis. Furthermore, all compounds were evaluated for the protective effects against hydrogen peroxide (H2O2)-induced injury in human hepatic L02 cells, for the inhibitory effects on nitric oxide (NO) production in RAW 264.7 cells, and for their cytotoxicity against three human cancer cell lines A549, HL60, and MCF7 in vitro. As a result, compounds 2, 4, 14 markedly weakened the oxidative damage induced by H2O2 in L02 cells via strengthening the cell viability.

Synthesis and characterization of two new mixed-ligand Cu(II) complexes of a tridentate NN'O type Schiff base ligand and N-donor heterocyclic co-ligands: In vitro anticancer assay, DNA/human leukemia/COVID-19 molecular docking studies, and pharmacophore modeling.

Two new mixed‐ligand complexes with general formula [Cu(SB)(L')]ClO4 (1 and 2) were synthesized and characterized by different spectroscopic and analytical techniques including Fourier transform infrared (FT‐IR) and UV–Vis spectroscopy and elemental analyses. The SB ligand is an unsymmetrical tridentate NN'O type Schiff base ligand that was derived from the condensation of 1,2‐ethylenediamine and 5‐bromo‐2‐hydroxy‐3‐nitrobenzaldehyde. The L' ligand is pyridine in (1) and 2,2′‐dimethyl‐4,4′‐bithiazole (BTZ) in (2). Crystal structure of (2) was also obtained. The two complexes were used as anticancer agents against leukemia cancer cell line HL‐60 and showed considerable anticancer activity. The anticancer activity of these complexes was comparable with the standard drug 5‐fluorouracil (5‐FU). Molecular docking and pharmacophore studies were also performed on DNA (PDB:1BNA) and leukemia inhibitor factor (LIF) (PDB:1EMR) to further investigate the anticancer and anti‐COVID activity of these complexes. The molecular docking results against DNA revealed that (1) preferentially binds to the major groove of DNA receptor whereas (2) binds to the minor groove. Complex (2) performed better with 1EMR. The experimental and theoretical results showed good correlation. Molecular docking and pharmacophore studies were also applied to study the interactions between the synthesized complexes and SARS‐CoV‐2 virus receptor protein (PDB ID:6LU7). The results revealed that complex (2) had better interaction than (1), the free ligands (SB and BTZ), and the standard drug favipiravir.

Multioxidized aromatic polyketides produced by a soil-derived fungus Penicillium canescens

Under OSMAC strategy, seven unreported multioxidized aromatic polyketides, penicanesins A‒G, were discovered from a soil-derived fungus Penicillium canescens along with seven known compounds. Their structures were assigned by extensive 1D and 2D NMR spectra in combination with HRESIMS and single crystal X-ray diffraction. Absolute stereochemistry of penicanesins A and D were elucidated by theoretical ECD calculation. (±)-Penicanesins A and B are two pairs of racemic aromatic polyketides with an unusual 6/6/6/6 heterotetracyclic ring core. In bioassay, (−)-penicanesin A shows potential cytotoxicity against human cancer cell lines HL-60 and SW480 with IC50 values at 13.8 ± 0.6 and 12.5 ± 0.9 μM, respectively, whereas the enantiomer (+)-penicanesin A is less active.

Investigation of Decitabine Effects on HDAC3 and HDAC7 mRNA Expression in NALM-6 and HL-60 Cancer Cell Lines.

Decitabine is a potent anticancer hypomethylating agent and changes the gene expression through the gene's promoter demethylation and also independently from DNA demethylation. So, the present study was designed to distinguish whether Decitabine, in addition to inhibitory effects on DNA methyltransferase, can change HDAC3 and HDAC7 mRNA expression in NALM-6 and HL-60 cancer cell lines. HL-60, NALM-6, and normal cells were cultured, and the Decitabine treatment dose was obtained (1 µM) through the MTT assay. Finally, HDAC3 and HDAC7 mRNA expression were measured by Real-Time PCR in HL-60 and NALM-6 cancerous cells before and after treatment. Furthermore, HDAC3 and HDAC7 mRNA expression in untreated HL-60 and NALM-6 cancerous cells were compared to normal cells. Our results revealed that the expression of HDAC3 and HDAC7 in HL-60 and NALM-6 cells increases as compared to normal cells. After treatment of HL-60 and NALM-6 cells with Decitabine, HDAC3, and HDAC7 mRNA expression were decreased significantly. Our data confirmed that the effects of Decitabine are not limited to direct hypomethylation of DNMTs, but it can indirectly affect other epigenetic factors, such as HDACs activity, through converging pathways.

Design, Synthesis, and Antipoliferative Activities of Novel Substituted Imidazole-Thione Linked Benzotriazole Derivatives.

A new series of benzotriazole moiety bearing substituted imidazol-2-thiones at N1 has been designed, synthesized and evaluated for in vitro anticancer activity against the different cancer cell lines MCF-7(breast cancer), HL-60 (Human promyelocytic leukemia), and HCT-116 (colon cancer). Most of the benzotriazole analogues exhibited promising antiproliferative activity against tested cancer cell lines. Among all the synthesized compounds, BI9 showed potent activity against the cancer cell lines such as MCF-7, HL-60 and HCT-116 with IC50 3.57, 0.40 and 2.63 µM, respectively. Compound BI9 was taken up for elaborate biological studies and the HL-60 cells in the cell cycle were arrested in G2/M phase. Compound BI9 showed remarkable inhibition of tubulin polymerization with the colchicine binding site of tubulin. In addition, compound BI9 promoted apoptosis by regulating the expression of pro-apoptotic protein BAX and anti-apoptotic proteins Bcl-2. These results provide guidance for further rational development of potent tubulin polymerization inhibitors for the treatment of cancer.

In Vitro Anti-proliferative Properties of Flavonoids Isolated from Artocarpus Heterophyllus on Cancer Cell Lines

: Artocarpus heterophyllus has been used as a folk medicine. This plant contained a wide range of flavonoid compounds and possessed several pharmacological properties including anticancer properties. Chemotherapeutic agent is a major option for cancer treatment. However, it may lead to tumor relapse. Therefore, it needs to discover an alternative to reduce this limitation using natural products. Objective: This study was aimed to determine anti-proliferative activities of isolated compounds against cancer cell lines. The morphological changes of cancer cell lines after treatment with the compounds was also evaluated. Methods: The flavonoid compounds were determined for their cytotoxic activity against leukaemia HL-60 (CCL-240), colorectal adenocarcinoma HT-29 (HTB-38), breast adenocarcinoma cancer MCF-7 (HTB-22), and non-small lung cancer H460 (HTB-177) cell lines using MTT assay. Hoechst 33342/PI staining assay was used to evaluate the morphological changes, and observed using a fluorescent microscope. Results: It showed that amongst compound, artocarpin consistently exhibited strong cytotoxic activity against H460, HT-29, MCF-7, and HL-60 cancer cell lines with IC50 values of 5.07, 5.56, 12.53, and 19.94 μg/mL, respectively. The activity was comparable to the cisplatin as a positive control. Morphological observations showed the most typical apoptotic morphology of cancer cells upon treatment with artocarpin and the least typical of apoptotic structure with other compounds. Conclusion: It can be suggested that A. heterophyllus bioactive compound modulates apoptosis by the presence of its distinctive, typical forms of morphological changes in treating cancer cells. Thus, artocarpin compound may provide high potential therapeutic use in chemotherapeutic strategies.

Bioactive secondary metabolites from a soybean-derived fungus Aspergillus versicolor IMBC-NMTP02

• Isolation of 10 compounds from Aspergillus versicolor IMBC-NMTP02. • Structural identification of 3 new, 2 new natural, and 5 known compounds. • Cytotoxicity toward HepG2, KB, HL-60, MCF-7, SK-Mel-2, and LNCaP cancer cells. • Nitric oxide inhibitory effects of the isolated compounds. • Antimicrobial effects of the isolated compounds. In the present study, 10 secondary metabolites, including three new asperversilactones A–C ( 2 , 4 , and 5 ) and two new natural metabolites (4 Z ,6 S ,7 R )-6,7-dihydroxyocta-2,4-dien-4-lactone ( 1 ) and (4 E ,6 S ,7 R )-6,7-dihydroxyocta-2,4-dien-4-lactone ( 3 ) were isolated from a culture fermentation of the soybean-derived fungus Aspergillus versicolor IMBC-NMTP02. Their structures were elucidated by comprehensive analyses of spectroscopic methods, including NMR, mass, and ECD spectra. Compounds 5 , 6 , and 9 were shown to have cytotoxic effects toward the HepG2, KB, HL-60, MCF-7, SK-Mel-2, and LNCaP human cancer cell lines (IC 50 = 31.7–81.5 μM), whereas all of the compounds inhibited NO overproduction in LPS-stimulated BV2 cells (IC 50 = 19.0–41.9 μM). Furthermore, all of the compounds showed antimicrobial effects against Enterococcus faecalis and Candida albican s, with MIC values in the range of 32–256 μM. Our investigation contributes to clarification of the chemical constituents of the soybean-derived A. versicolor and warrants further studies of some bioactive metabolites for therapeutic uses.

Synthesis, Characterization, and Biological Study of 3-Trifluoromethylpyrazole Tethered Chalcone-Pyrrole and Pyrazoline-Pyrrole Derivatives.

The present study illustrates the design and synthesis of new series of 3-trifluoromethylpyrazole tethered chalcone-pyrrole and pyrazoline-pyrrole derivatives. All compounds were further screened for in vitro cytostatic activities on full NCI 60 cancer cell lines at National Cancer Institute, USA. Compounds (2E)-3-(1H-pyrrol-2-yl)-1-{4-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}prop-2-en-1-one (5a) and (2E)-1-{3-methyl-4-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}-3-(1H-pyrrol-2-yl)prop-2-en-1-one (5c) displayed significant antiproliferative activity (Growth Percentage: -77.10 and -92.13, respectively at 10 μM concentration) against the UO-31 cell lines from renal cancer and were further selected for assay at 10-fold dilutions of five different concentrations (10-4 to 10-8 M). Both compounds 5a and 5c exhibited promising antiproliferative activity (GI50 : 1.36 to 0.27 μM) against leukemia cancer cell lines HL-60 and RPMI-8226, colon cancer cell lines KM-12; breast cancer cell lines BT-549. Moreover, both compounds 5a and 5c were found to be non-cytotoxic (LC50 >100) against HL-60, RPMI-8226, and KM-12 cell lines. Remarkably, GI50 values of compounds 5a and 5c were identified as more promising than sunitinib against most cancer cell lines. In silico study of compounds 5a and 5c exemplified the desired ADME properties for drug-likeness as well as tighter interactions with VEGFR-2. Hence, compounds 5a and 5c would be good cytotoxic agents after further clinical study.

Trans-palladium complexes with 1-adamantanamine and various halide ions: Synthesis, characterization, DNA and protein binding and in vitro cytotoxicity

Research into the antitumor effects of transition metals has been devoted to the decades since the discovery of the cytostatic properties of the platinum complex cisplatin, which despite numerous side effects, is still one of the most prescribed cytostatics. A promising way to develop a new similar complex is to select a suitable ligand. An interesting group of ligands is diamantanoid derivatives, which, due to their high lipophilicity and bulk, show promising pharmacological properties. With this in mind, we have prepared three trans-palladium(II) complexes with bulky 1-adamantanamine and different halide ligands (chlorine, bromine and iodine). The complexes (1–3) were analytically characterized to confirm their structures by FT-IR, 1H and 13C NMR, HR-MS and XRD techniques for the first time. The interaction of DNA with complexes 1–3 was investigated and the affinity to DNA was confirmed by a DNA binding study, gel electrophoresis and electronic circular dichroism. A protein binding study was carried out and a weak interaction with proteins was found. Finally, the anticancer abilities of palladium complexes 1–3, compared to another cytostatic drug oxaliplatin, were tested and confirmed on the cancer cell lines RAW, HeLa, HOC and HL-60, and the healthy cell line MRC-5.

Homoisoflavonoids from the tuberous roots of Ophiopogon japonicus with their cytotoxic activities

Two new homosioflavonoids, ophiopogonanone I (1) and methylophiopogonanone C (2) were isolated from the tuberous roots of Ophiopogon japonicus. Their structures were elucidated on the basis of extensive spectroscopic analyses. The absolute configuration of compounds 1 and 2 were assigned on the basis of CD method. In addition, compounds 1–2 were tested for their cytotoxic activities against HL-60, SMMC-7721, and MCF-7 human cancer cell lines, and compound 2 showed significant cytotoxic activity against HL-60 cell line with IC50 value of 14.42 μM.

Dimeric 9,10-dihydrophenanthrene derivatives from Bletilla striata and their atropisomeric nature

Four pairs of undescribed racemic bi(9,10-dihydro) phenanthrene and phenanthrene/bibenzyl atropisomers, bletistriatins A-D (1–4), along with 22 known compounds were isolated from the rhizomes of Bletilla striata. These dimeric derivatives were constructed through direct C–C connection or an oxygen bridge. The structures of new compounds were fully established by extensive analysis of MS, and 1D and 2D NMR spectroscopic data. Owing to sterically hindered rotation around the biaryl axis, these dimeric 9,10-dihydrophenanthrene derivatives can exist as a pair of enantiomers, but were isolated as racemates. Their racemates were separated to yield enantiomerically pure compounds by HPLC on an optically active stationary phase, and were stereochemically characterized on-line by circular dichroism (CD) spectroscopy (LC-CD coupling). Some isolates were evaluated for cytotoxicity against human cancer cell lines HL-60 and A549. Compounds 13, 17, and 20 showed cytotoxicity against HL-60 and A-549 cell lines with IC50 values ranging from 2.56 to 8.67 μM.

Longipone A, a unique tricyclic polyketide from the fungus Xylaria longipes

Longipone A (1), a novel polyketide containing a tetrahydro-anthracene core structure, was isolated from the liquid fermentation of fungus Xylaria longipes. Its structure, including absolute configuration, was determined on the basis of spectroscopic data and X-ray crystallography. A plausible biosynthesis pathway has also been proposed. This compound exhibited moderate cytotoxicity (IC50 10.3–35.2 μM) against HL-60, A549, MCF-7 and SW480 human cancer cell lines.

Toxicological and Epigenetic Studies of Two Types of Ale Beer, Tyrosol and Iso-Alpha Humulone

Although many benefits drawn from beer consumption are claimed, the epidemiological records are contradictory with respect to cancer prevention. The purpose of this study was to investigate the possible health-related activities involving genome safety and the ageing processes of two types of lyophilised ale beers (blond and stout), as well as two of their bioactive compounds (tyrosol and iso-alpha humulone). A multipurpose trial set of in vivo toxicity, antitoxicity, mutagenicity, antimutagenicity, lifespan and healthspan assays using Drosophila melanogaster were used. In parallel, several in vitro assays were designed using the cancer cell line HL-60 in order to establish the possible chemopreventive activity of the selected substances, where epigenetic modulation of DNA methylation changes, clastogenic activity and tumour cell inhibition growth were evaluated. The safety of the four substances was confirmed: lyophilised blond ale beer (LBAB), lyophilised stout ale beer (LSAB), tyrosol and iso-alpha humulone were neither toxic nor genotoxic. Moreover, all substances, except tyrosol, revealed the ability to protect individual genomes against oxidative radicals and to exert antimutagenic activity against the genotoxin hydrogen peroxide. With respect to the degenerative process indicators of lifespan and healthspan, tyrosol was the only compound that did not exert any influence on the life extension of Drosophila; LBAB induced a significant lifespan extension in D. melanogaster; LSAB and its distinctive compound iso-alpha humulone induced a reduction in longevity. The in vitro assays showed the cytotoxic activity of LBAB, LSAB and tyrosol against HL-60 cells. Moreover, proapoptotic DNA fragmentation or DNA strand breakage was observed for both types of beers and iso-alpha humulone at different concentrations. Furthermore, the lyophilised ale beers and tyrosol exhibited an increasing genome-wide methylation status, while iso-alpha humulone exhibited a demethylation status in repetitive cancer cell sequences. Although the biological activities assigned to beer consumption cannot be linked to any specific molecule/element due to the complexity of the phenolic profile, as well as the multifactor brewing process, the results obtained let us propose lyophilised ale beers as safe potential nutraceutical beverages when consumed in moderate amounts. The prevention of toxicity and genetic oxidative damage, as well as the induction of tumor cell death and modulation of the methylation status, are the key activities of beer that were shown in the present research.

Total Synthesis and Conformational Analysis of Naturally Occurring Lipovelutibols along with Lead Optimization of Lipovelutibol D.

Four lipopeptaibols, namely, lipovelutibols A–D, were recently isolated from psychrotrophic fungus Trichoderma velutinum and reported to have significant cytotoxic activity against HL-60, MDA-MD-231, A549, and LS180 cancer cell lines. In the present study, these peptides were synthesized in a solution using a segment condensation approach. The conformational analysis of these peptides carried out using CD spectrophotometry revealed the formation of 310-helix, and the NMR-VT experiments showed intramolecular hydrogen bonding for NH-5, NH-6, and NH-7. Lipovelutibol D showed potent cytotoxic activity and was chosen for lead optimization. It involved N- and C-terminal truncation, N- and C-terminal modification, random deletion, l/d configuration replacement, and other synthetic analogues. These were tested against various breast cancer cell lines. The C-terminal aldehyde analogue resulting from lead optimization of lipovelutibol D was found to have almost twofold enhanced cytotoxicity against MDA-MB-231 breast cancer cell lines.

3,7-bis-benzylidene hydrazide ciprofloxacin derivatives as promising antiproliferative dual TOP I & TOP II isomerases inhibitors

We report herein design and synthesis of a new series of 3,7-bis-benzylidenes of ciprofloxacin. Most of the target compounds revealed good cytotoxic activity; the most potent 4e and 4i achieved strong broad spectrum antiproliferative activity with comparable activity to Doxorubicin with IC50 (µM) of 1.21 ± 0.02, 0.87 ± 0.04, 1.21 ± 0.02; 0.41 ± 0.02, 0.57 ± 0.06, 1.31 ± 0.04 and 1.26 ± 0.01, 1.79 ± 0.04, 0.63 ± 0.01 against leukemia cancer cell line HL-60 (TB), colon cancer cell line HCT-116 and breast cancer cell line MCF7, respectively. Moreover, the most potent derivative 4i induced apoptosis at G2/M phase Investigating the mechanism of action of compounds 4e, 4 h and 4i exhibited promising dual TOP Iα and TOP IIB % inhibition comparable to Camptothecin and Etoposide; respectively. Docking of 4e, 4 h and 4i into the active site of topo I and II proteins compared to Camptothein and Etoposide revealed acceptable binding score and augmented enzyme assay data. Hence, 4e and 4i are promising targeted antiproliferative dual acting TOP Iα TOP IIB inhibitors that require further optimization.

The Effects of Combining Cancer Drugs with Compounds Isolated from Combretum zeyheri Sond. and Combretum platypetalum Welw. ex M.A. Lawson (Combretaceae) on the Viability of Jurkat T Cells and HL-60 Cells.

Combretum zeyheri and Combretum platypetalum have been shown to have anticancer, antibacterial, antituberculosis, and antifungal effects in both in vivo and in vitro studies. This study sought to evaluate the antiproliferative effects of compounds isolated from C. zeyheri and C. platypetalum on Jurkat T and HL-60 cancer cell lines in combination with doxorubicin and/or chlorambucil. At their GI50 concentrations, the isolated compounds were combined with the corresponding GI50 of chlorambucil and doxorubicin. The cytotoxic effects of the combined compounds were determined on BALB/c mouse peritoneal cells. All the 4 isolated compounds had significant cytotoxic effects on Jurkat T cells. Compounds CP 404 (1), CP 409 (2), CZ 453 (3), and CZ 455 (4) had GI50s on Jurkat T cells of 3.98, 19.33, 6.82, and 20.28 μg/ml, respectively. CP 404 (1), CP 409 (2), CZ 453 (3), and CZ 455 (4) showed GI50s of 14.18, 28.69, 29.87, and 16.46 μg/ml on HL-60 cancer cell lines, respectively. The most potent combination against Jurkat T cells was found to be CP 404 (1) and chlorambucil. This combination showed no cytotoxic effects when tested on BALB/c mouse peritoneal cells. It was concluded that the compounds extracted from C. zeyheri and C. platypetalum inhibit the growth of Jurkat T cells in vitro. The combination of the compounds with anticancer drugs enhanced their anticancer effects. The combination of CP 404 (1) and chlorambucil was found not to be toxic to normal mammalian cells. Therefore, CP 404 (1), 3-O-β-L-rrhamnopyranosyl-5,7,3′4′,5′-pentahydroxyflavone, has the potential to be a source of lead compounds that can be developed for anticancer therapy. Further structure-activity relationship studies on this compound are warranted.

Novel Amides Derivative with Antimicrobial Activity of Piper betle var. nigra Leaves from Indonesia.

Piper betle var. nigra is a tropical plant closely related to the common piper. P. betle has also been dubbed a promising source of natural antioxidants in herbal health products, antibacterial, antifungal, antimalarial, cytotoxic activity against the cancer cell lines K562 and HL-60, and antileishmanial. The aim of this study to observation Antimicrobial activity and isolation of chemical compound. The antimicrobial activity of P. betle extract was performed by well diffusion method against two oral pathogenic bacteria (Streptococcus mutans and Streptococcus sanguinis) and opportunistic pathogenic yeast (Candida albicans). The inoculum (bacterial and yeast suspension) was prepared from a 24-h culture on NB for bacterial suspension and on TSB for yeast suspension. Extraction and isolation using various method of chromatography. Isolated compounds were characterized by spectroscopic means. Our study showed antimicrobial activity from crude ethanol extract of leaves P. betle L. var. nigra against two oral pathogenic bacteria and opportunistic pathogenic yeast with concentration 0.5% and 1%. The first report of two new amides derivatives, piperenamide A (1) and piperenamide B (2) in P. betle L. var. nigra.

Armochaetoglasins J and K: new cytochalasans from Chaetomium globosum

Two novel cytochalasans, armochaetoglasin J (1) and armochaetoglasin K (2), along with 14 known analogues (3−16) were isolated from Chaetomium globosum. Their structures were elucidated by HRESIMS, NMR spectroscopy, single-crystal X-ray crystallography, and ECD spectra. Armochaetoglasins J and K were found to be inactive against the HepG2, HT-29, K562, HL-60, and A549 cancer cell lines.

QSAR Classification of Anticancer Heterocyclichydrazones With Reactivity Descriptors

In this study, validated PLS-DA models that discriminate heterocyclichydrazones with potent anticancer activity (GI50/IC50<50x10-6M) from those with low activity (GI50/IC50>=50x10-6M) against the cancer cell lines HCT-116 (colon), OVCAR-8 (human ovary), HL-60 (leukemia), and SF-295 (glioblastoma) were developed. A dataset of 24-a-(N)-heterocyclichydrazones and 14 N-acylhydrazonyl-thienyl and various global and local reactivity descriptors were used for modeling. The best models classified for training and test sets with an accuracy range between 67-100%, a class specificity and sensitivity range between 71-100%, error rate range between 0-0.27, and non-error rate range between 0.73-1.0. An external set of 20 compounds was predicted and the models showed which new compounds are not suggested for further biological investigation. The molecular properties with impact on the modeled endpoints show that the antitumor activity can be improved with electron-acceptor N-acylhydrazonyl-thienyl derivatives and a-(N)-heterocyclichydrazones with moderate electron-donating character.