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Growing mushrooms means meeting challenges while aiming for sustainability and circularity. Wherever the producer is located, commercial strains are the same originating from several producers. Customized strains adapted to local conditions are urgently needed. Before introducing new species to the strain development pipeline, the chemical characterization and biological activity of wild ones need to be assessed. Accordingly, the mycoceutical potential of five polypore mushroom species from Serbia was evaluated including: secondary metabolite composition, oxidative damage prevention, anti-tyrosinase, and anti-angiotensin converting enzyme (ACE). The phenolic pattern was comparable in all samples, but the amounts of specific chemicals varied. Hydroxybenzoic acids were the primary components. All samples had varying quantities of ascorbic acid, carotene, and lycopene, and showed a pronounced inhibition of lipid peroxidation (LPx) and ability to scavenge HO•. Extracts were more potent tyrosinase inhibitors but unsuccessful when faced with ACE. Fomitopsis pinicola had the strongest anti-tumor efficacy while Ganoderma lucidum demonstrated strong selectivity in anti-tumor effect in comparison to normal cells. The evaluated species provided a solid foundation for commercial development while keeping local ecology in mind.

Growing mushrooms is meeting challenges while aiming for sustainability and circularity. Wherever the producer is located, commercial strains are the same originating from several producers. Following the harvest, enormous quantities of spent mushroom substrate containing spores are disposed presenting a type of foreign material pressure on the ecosystem in the form of the loss of genetic diversity in wild mushroom populations. This challenge can be mitigated by bioprospecting local strains and using them to generate commercial inoculum. Accordingly, the mycoceutical potential of five polypore mushroom species from Serbia was evaluated: secondary metabolite composition, oxidative damage prevention, anti-tyrosinase, and antiangiotensin converting enzyme (ACE) properties. The phenolic pattern was comparable in all samples, but the amounts of specific chemicals varied. Hydroxybenzoic acids were the primary components. All samples had varying quantities of ascorbic acid, carotene, and lycopene, and showed a pronounced inhibition of lipid peroxidation (LPx) and ability to scavenge HO•. Extracts were more potent tyrosinase inhibitors but unsuccessful when faced with ACE. Fomitopsis pinicola had the strongest anti-tumor efficacy while Ganoderma lucidum demonstrated strong selectivity in anti-tumor effect in comparison to healthy cells. The evaluated species provided a solid foundation for commercial development while keeping the local ecology in mind.

Growing mushrooms is meeting challenges while aiming for sustainability and circularity. Wherever the producer is located, commercial strains are the same originating from several producers. Following the harvest, enormous quantities of spent mushroom substrate containing spores are disposed presenting a type of foreign material pressure on the ecosystem in the form of the loss of genetic diversity in wild mushroom populations. This challenge can be mitigated by bioprospecting local strains and using them to generate commercial inoculum. Accordingly, the mycoceutical potential of five polypore mushroom species from Serbia was evaluated: secondary metabolite composition, oxidative damage prevention, anti-tyrosinase, and antiangiotensin converting enzyme (ACE) properties. The phenolic pattern was comparable in all samples, but the amounts of specific chemicals varied. Hydroxybenzoic acids were the primary components. All samples had varying quantities of ascorbic acid, carotene, and lycopene, and showed a pronounced inhibition of lipid peroxidation (LPx) and ability to scavenge HO•. Extracts were more potent tyrosinase inhibitors but unsuccessful when faced with ACE. Fomitopsis pinicola had the strongest anti-tumor efficacy while Ganoderma lucidum demonstrated strong selectivity in anti-tumor effect in comparison to healthy cells. The evaluated species provided a solid foundation for commercial development while keeping the local ecology in mind.

Several coumarin derivatives with a directly attached azole substituent at C‐4 were synthesized and biologically studied for their anticancer properties. The cell lines used for this investigation (HeLa, K‐562, MDA‐MB‐53, and MCF‐7) demonstrated different sensitivities. The best response in the MTT (3‐(4,5‐dimethyl‐2‐thiazolyl)‐ 2,5‐diphenyl‐2H‐tetrazolium bromide) assay was shown by K‐562 cells, with compounds displaying activity (3c, IC50 3.06 μM; 4a, IC50 5.24 μM; 4c, IC50 4.7 μM) similar to that of cisplatin (IC50 ~6 μM), which was used as the standard. The studied azole‐substituted coumarins demonstrated weaker activity toward other cell lines, except for compound 4c, which was equally potent in the case of MCF‐7 cells. Additional biological evaluations supported interference with the cell cycle as a potential mechanism of action and confirmed the absence of toxicity in zebrafish embryos. On the basis of these initial results, 4‐azole coumarins should be explored further. Although their activity would need additional optimization, the fact that these compounds are fragment‐like structures with MW <300 and clog P <3 offers enough flexibility to fine‐tune their drug‐like properties.

Tetrahydropyrimidines are a class of azaheterocycles, also called Biginelli hybrids (obtained from the Biginelli reaction), that have attracted an enormous interest in the medicinal chemistry community in recent years, due to a broad biological activity, such as anticancer, antiviral, anti-inflammatory, antidiabetic, antituberculosis activities, etc. According to SciFinder®, more than 70 000 different Biginelli-like compounds have been covered in publications. However, although the Biginelli reaction can yield a large number of compounds with a broad range of activities, none of them have been captured in a carrier. In this study, chitosan-based (Ch) nanoparticles (NPs) containing three different molecules (Biginelli hybrids) were developed and tested for the first time as simple and promising vehicles for anticancer Biginelli-based drugs. The key features of NPs, such as size, surface morphology, drug encapsulation efficiency, and in vitro release were systematically investigated. Rather weak cell selectivity of pure Biginelli hybrids (A–C) to selected cancer cell lines has improved and this has been accompanied with two-to-four times stronger cytotoxic effect of A–C loaded Ch NPs, with a triple reduction in toxicity to healthy cells (MRC-5). It has been observed that the examined NPs induce apoptosis. The cell cycle analysis has confirmed the influence of A-loaded Ch (A-Ch), B-loaded Ch (B-Ch), and C-loaded Ch (C-Ch) on the cell cycle distribution, which was homogenously affected. This is the difference with regard to the effect of A, B, and C on the cell cycle. It has been established that the increased selectivity and antitumor activity of NPs are related to the presence of the carrier.

H and 13C NMR spectra

Two new complexes with the general formula [Cu2(L)tpmc](ClO4)3·nH2O (tpmc = N,N′,N′′,N′′′-tetrakis(2-pyridylmethyl)- -1,4,8,11-tetraazacyclotetradecane, L = N-methylglycine, n = 3; L = N,N- -dimethylglycine, n = 2) were isolated and their composition, some physical and chemical properties and geometries were proposed based on elemental analysis (C, H, N), conductometric and magnetic measurements and spectro-scopic data (UV–Vis, FTIR). It is evident that the complexes are binuclear and an exo coordination mode of the macrocyclic ligand in the boat conformation was proposed. The co-ligands are coordinated as a bridge using both oxygen atoms of the OCO- group. The cytotoxic activity of Cu(II) complexes as well as their Co(II) analogs, the starting ligands and the free salts were tested against human cervix adenocarcinoma cell line (HeLa), human chronic myelo-genous leukemia cells (K562), human breast cancer cell line (MDA-MB-453), and a non-cancerous cell line, human embryonic lung fibroblast (MRC-5). The IC50 values for the Cu(II) complexes were from 21.6±0.04 to 66.1±0.8, and for the Co(II) analogs were within the range from 8.8±0.74 to 15.40±1.52. All four complexes were tested for their antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and the yeast Candida albicans.

Gljive su izvor raznih farmakološki aktvinih komponenti zahvaljujući čemu su postale predmet ospežnih istraživanja u poslednjih nekoliko decenija. Lekovite gljive korsitili su mnogi narodi širom sveta, a naročito dalekog istoka, hiljadama godina, ali je tek s razvojem analitike bilo moguće okarakterisati njihovo dejstvo. Ipak, mnoge gljive i dalje su ostale relativno nepoznate u pogledu svog farmakološkog potencijala., Fungi are source of various pharmacologiacally active compounds and they have been a subject of extensive study in a past few decades. Medicinal mushrooms were used in traditional medicine in many parts of the world, especially in the far east, and such use goes back to few thousand years. Modern analytical technologies allowed the characterisation of the medicinal proteperties of mushrooms. Still, many fungi species remain unsufficiently studied...

Fungi are source of various pharmacologiacally active compounds and they have been a subject of extensive study in a past few decades. Medicinal mushrooms were used in traditional medicine in many parts of the world, especially in the far east, and such use goes back to few thousand years. Modern analytical technologies allowed the characterisation of the medicinal proteperties of mushrooms. Still, many fungi species remain unsufficiently studied..., Gljive su izvor raznih farmakološki aktvinih komponenti zahvaljujući čemu su postale predmet ospežnih istraživanja u poslednjih nekoliko decenija. Lekovite gljive korsitili su mnogi narodi širom sveta, a naročito dalekog istoka, hiljadama godina, ali je tek s razvojem analitike bilo moguće okarakterisati njihovo dejstvo. Ipak, mnoge gljive i dalje su ostale relativno nepoznate u pogledu svog farmakološkog potencijala.

Methanol extracts of mosaic puffball (Handkea utriformis, Bovistella utriformis, Lycoperdon utriforme, Calvatia utriformis - current name is a subject of debate), from three different stages - mycelium (HUMIC), immature (HUI) and mature fruiting bodies (HUM) were characterized and tested for antioxidant, antimicrobial and inhibitory activity on tyrosinase, acetyholinesterase (AChE), butyrylcholinesterase (BuChE) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA-R). Immature, edible, fruiting bodies were shown to be a good source of antioxidants (11.5 mg/g of extract) and cholesterol-lowering agent, lovastatin (234 mu g/g of extract), and exhibited significant antimicrobial activity. In addition, HUI showed good and selective AChE (4.48 mg/mL) and non-lovastatin related HMG-CoA-R inhibition (1.16 mg/mL), which all together suggests that regular consumption of it may have health benefits. Mature fruiting bodies, inedible due to powdery consistence, have been used in traditional medicine for wound treatment; their extract was relatively rich in free ergosterol (31.65 mg/g of extract), N-acetylglucosamine (24 mg/g of extract), alpha-tocopherol (4 mg/g of extract) and had best overall antioxidant activity, which was in correlation with its highest phenolic content (19.4 mg GAE/mL). It also exhibited significant tyrosinase inhibitory activity (0.22 mg/mL) and thus could be used in medicinal and cosmetic products for wound healing and bleaching. Mycelium, which can be easily grown in laboratory conditions did not have the same properties as, neither immature or mature fruiting bodies, although it showed prominent antimicrobial activity, notably against Pseudomonas aeruginosa (MIC = 0.0625 mg/mL) and could be a source of antimicrobial compounds.

The synthesis of a new endodontic mixture based on calcium aluminate cement is reported. Physico-chemical and mechanical properties of the mixture were investigated before and after various hydration periods. Phase analysis of the mixture was performed using X-ray diffraction (XRD), while morphological analysis was performed by scanning electron microscopy (SEM) equipped with EDS which revealed elemental composition of the mixture sample. Investigations of mechanical properties showed that this new endodontic mixture possessed good mechanical properties (compressive strength after 28 days aging was 94 MPa) and relatively short setting time (2 h). Additionally, cytotoxicity of the mixture was investigated by MTT assay, while genotoxicity was investigated by Comet assay, using MRC-5 cell line. The obtained results make this material very promising for potential application in dental practice. © 2019 Elsevier Ltd and Techna Group S.r.l.

A novel triphenyltin(IV) compound with 1-(4-carboxyphenyl)-3-ethyl-3-methylpyrrolidine-2,5-dione was synthesized and characterized by IR, NMR spectroscopy, mass spectrometry, and elemental analysis. In vitro anticancer activity of ligand precursor and synthesized organotin(IV) compound was determined against tumor cell lines: human adenocarcinoma (HeLa), human myelogenous leukemia (K562), and human breast cancer (MDA-MB-453), using microculture tetrazolium test (MTT) assay. The results indicate that complex exhibited very high antiproliferative activity against all tested cell lines with IC 50 values in the range of 0.22 to 0.53 µ M. The highest activity organotin(IV) compound expressed against the HeLa cells (IC 50 = 0.22 ± 0.04 µ M). The ligand precursor did not show anticancer activity (IC 50 > 200 µ M). Furthermore, fluorescence microscopy analysis of HeLa cells reveal that organotin(IV) complex induced apoptosis as a mode of cell death, which is consistent with the increase of cells in the sub-G1 phase.

Antiproliferative and antibacterial activities of nine glutarimide derivatives (1–9) were reported. Cytotoxicity of compounds was tested toward three human cancer cell lines, HeLa, K562 and MDA-MB-453 by MTT assay. Compound 7 (2-benzyl-2-azaspiro[5.11]heptadecane-1,3,7-trione), containing 12-membered ketone ring, was found to be the most potent toward all tested cell lines (IC50 = 9–27 μM). Preliminary screening of antibacterial activity by a disk diffusion method showed that Gram-positive bacteria were more susceptible to the tested compounds than Gram-negative bacteria. Minimum inhibitory concentration (MIC) determined by a broth microdilution method confirmed that compounds 1, 2, 4, 6–8 and 9 inhibited the growth of all tested Gram-positive and some of the Gram-negative bacteria. The best antibacterial potential was achieved with compound 9 (ethyl 4-(1-benzyl-2,6-dioxopiperidin-3-yl)butanoate) against Bacillus cereus (MIC 0.625 mg/mL; 1.97 × 10−3 mol/L). Distinction between more and less active/inactive compounds was assessed from the pharmacophoric patterns obtained by molecular interaction fields.

Handkea utriformis (HU), H. excipuliformis (HE) and Vascellum pratense (VP) mature fruiting bodies methanol extracts were tested for biological activities and active compounds. The extracts showed prominent radical scavenging, reducing, antioxidative and chelating abilities. Scavenging ability was correlated with phenolic (ABTS assay) or phenolic and/or sugar/beta-glucan content (DPPH). Antioxidative and Fe3+-reducing ability of VP extract was the highest, and was best correlated with flavonoid content. The same extract exhibited the best angiotensin-converting enzyme inhibitory activity. HU and HE showed selectivity toward tumor cell lines in cytotoxicity analysis. The extracts exhibited various antimicrobial activity, the best being against Listeria monocytogenes (HE, MIC-0.625 mg/mL); fatty acid content was particularly high in HU (37.25 mg/g), with linoleic acid making up more than 57% in all samples. Phenolics were present in considerable amount, as well as beta-glucans (HU, 16.67%). Although these mushrooms are inedible after autolysis process, they were still a good source of biologically active products.

Partially purified polysaccharides (FP) and hot alkali extract (FNa) obtained from fruiting bodies of the wild basidiomycete Grifola frondosa were examined for their antimicrobial, antioxidant and cytotoxic activity. The structural properties of FP and FNa samples were investigated by FT-IR and high resolution 1H- and 13C-NMR spectroscopy. From a group of various G- and G+ bacteria the antibacterial effects were highest against the G + B. cereus. FNa was the better antioxidant shown by the lower EC50 values of DPPH scavenging ability, ferric-reducing antioxidant power and ferrous ion-chelating ability. Ferric-reducing antioxidant power and ferrous ion-chelating ability were mostly linked to total polysaccharides, total- and beta-glucan content, as well as total protein content. Both extracts displayed a moderate dose dependent antiproliferative action towards malignant human breast cancer MDA-MB-453, cervical adenocarcinoma HeLa and myelogenous leukemia K562 cells not observed in the non cancer derived MRC-5 fibroblasts. The highest effect was found in HeLa cells for FP extract. The mean diameter of Ca-alginate bead loading FP was 960.7 mu m while the mean diameter of beads encapsulating FNa extract was 1051.7 mu m.

The methanolic extract of the wild edible mushroom Cantharellus cibarius Fr. (chanterelle) was analyzed for in vitro antioxidative, cytotoxic, antihypertensive and antibacterial activities. Various primary and secondary metabolites were found. Phenols were the major antioxidant components found in the extract (49.8 mg g(-1)), followed by flavonoids, whose content was approximately 86% of the total phenol content. Antioxidant activity, measured by four different methods, was high for inhibition of lipid peroxidation (EC50 = 1.21 mg mL(-1)) and chelating ability (EC50 = 0.64 mg mL(-1)). The antioxidant activity of the C. cibarius methanol extract was achieved through chelating iron compared to hydrogen atom and/or electron transfer. The extract showed good selectivity in cytotoxicity on human cervix adenocarcinoma HeLa, breast carcinoma MDA-MB-453 and human myelogenous leukemia K562, compared to normal control human fetal lung fibroblasts MRC-5 and human lung bronchial epithelial cells BEAS-2B. The extract had inhibitory activity against angiotensin converting I enzyme (ACE) (IC50 = 0.063 mg mL(-1)). The extract revealed selective antimicrobial activity against Gram-positive bacteria with the highest potential against E. faecalis. The medicinal and health benefits, observed in wild C. cibarius mushroom, seem an additional reason for its traditional use as a popular delicacy food.

The birch polypore Piptoporus betulinus was among two mushrooms that were found in the Iceman's bag. Recent studies indicated that P. betulinus was probably used as a religious and medicinal item. In order to examine the medicinal potential of P. betulinus, hot water (HW), partially purified (PP), and alkali extract (HA) were prepared and tested for antioxidant, antimicrobial, cytotoxic, and angiotensin I-converting enzyme (ACE) inhibitory activity. All tested samples exhibited moderate cytotoxic activity, and HW appeared as the most effective (IC50 = 0.8 +/- 0.1 mg/ml for HeLa cells). HA proved to be a good 1,1-diphenyl-2-picrylhydrazyl radical scavenger and exhibited the strongest ferric-reducing power (EC50 = 0.07 +/- 0.3 mg/ml). The same extract (HA) also expressed the strongest ferric-reducing power (EC50 = 0.99 +/- 0.1 mg/ml). Hot alkali extraction contributed significantly to ACE inhibitory activity (EC50 = 0.06 +/- 0.00 mg/ml) and to antimicrobial activity, especially against highly resistant Enterococcus faecalis (minimum inhibitory concentration: 0.156 +/- 0.000 mg/ml; and minimum bactericidal concentration: 1.25 +/- 0.00 mg/ml).

Series of twelve chalcone and propafenone derivatives has been synthesized and evaluated for anticancer activities against Hela, Fem-X, PC-3, MCF-7, LS174 and K562 cell lines. The 2D-QSAR and 3D-QSAR studies were performed for all compounds with cytotoxic activities against each cancer cell line. Partial least squares (PLS) regression has been applied for selection of the most relevant molecular descriptors and QSAR models building. Predictive potentials of the created 2D-QSAR and 3D-QSAR models for each cell line were compared, by use of leave-one-out cross-validation and external validation, and optimal QSAR models for each cancer cell line were selected. The QSAR studies have selected the most significant molecular descriptors and pharmacophores of the chalcone and propafenone derivatives and proposed structures of novel chalcone and propafenone derivatives with enhanced anticancer activity on the HeLa, Fem-X, PC-3, MCF-7, LS174 and K562 cells.

Cinnamic acid derivatives can be found in plant material, and they possess a remarkable variety of biological effects. In the present study, we have investigated the cytotoxic effects of representative cinnamic acid esters and amides. The cytotoxicity was determined by MTT test on human cervix adenocarcinoma (HeLa), myelogenous leukemia (K562), malignant melanoma (Fem-x), and estrogen-receptor-positive breast cancer (MCF-7) cells, versus peripheral blood mononuclear cells (PBMCs) without or with the addition of the plant lectin phytohemaglutinin (PHA). The compounds tested showed significant cytotoxicity (IC(50)s between 42 and 166 mu M) and furthermore selectivity of these cytotoxic effects on the malignant cell lines versus the PBMCs was also seen, especially when electron-withdrawing groups, such as a cyano group (compound 5), were present on the aromatic rings of the alcohol or amine parts of the cinnamic acid derivatives. The additional study on cell cycle phase distribution indicated that novel cinnamic acid derivatives inhibit cell growth by induction of cell death. Thus, cinnamic acids derivatives represent important lead compounds for further development of antineoplastic agents.

Background: The aim of this research was to determine the intensity and mechanisms of the cytotoxic actions of five extracts isolated from the endemic plant species Helichrysum zivojinii Cernjavski & Soska (family Asteraceae) against specific cancer cell lines. In order to evaluate the sensitivity of normal immunocompetent cells implicated in the antitumor immune response, the cytotoxicity of extracts was also tested against healthy peripheral blood mononuclear cells (PBMC). Methods: The aerial parts of the plants were air-dried, powdered, and successively extracted with solvents of increasing polarity to obtain hexane, dichloromethane, ethyl-acetate, n-butanol and methanol extracts. The cytotoxic activities of the extracts against human cervix adenocarcinoma HeLa, human melanoma Fem-x, human myelogenous leukemia K562, human breast adenocarcinoma MDA-MB-361 cells and PBMC were evaluated by the MTT test. The mode of HeLa cell death was investigated by morphological analysis. Changes in the cell cycle of HeLa cells treated with the extracts were analyzed by flow cytometry. The apoptotic mechanisms induced by the tested extracts were determined using specific caspase inhibitors. Results: The investigated Helichrysum zivojinii extracts exerted selective dose-dependent cytotoxic actions against selected cancer cell lines and healthy immunocompetent PBMC stimulated to proliferate, while the cytotoxic actions exerted on unstimulated PBMC were less pronounced. The tested extracts exhibited considerably stronger cytotoxic activities towards HeLa, Fem-x and K562 cells in comparison to resting and stimulated PBMC. It is worth noting that the cytotoxicity of the extracts was weaker against unstimulated PBMC in comparison to stimulated PBMC. Furthermore, each of the five extracts induced apoptosis in HeLa cells, through the activation of both intrinsic and extrinsic signaling pathways. Conclusion: Extracts obtained from the endemic plant Helichrysum zivojinii may represent an im

Uvod: Pronalaženje agenasa sa potencijalnim antitumorskim dejstvom je imperativ u modernoj onkologiji. Pri tome se sve više zapaža da određene hemijske strukture imaju specifičnije toksično dejstvo na maligne ćelije. Otkriće artemizinina je označilo početak istraživanja peroksida kao potencijalne zamene za tradicionalne antimalarijske lekove, a iz ovih istraživanja nastala je i strukturno jednostavna klasa peroksida - 1,2,4,5-tetraoksani, za koje je ubrzo pokazano da pored antimalarijskog pokazuju i snažan antiproliferativni efekat. Maligne ćelije imaju poremećaje u regulatornim mehanizmima koji upravljaju ćelijskom proliferacijom i homeostazom. Sposobnost tumorskih ćelijskih populacija da povećaju broj ćelija je određena ne samo intenzitetom ćelijske proliferacije, već i brzinom uklanjanja ćelija. Programirana ćelijska smrt - apoptoza, predstavlja glavni izvor ovog uklanjanja. Cilj rada je bio da se odredi nivo citotoksičnog dejstva grupe mešovitih tetraoksana prema različitim humanim malignim ćelijama, kao i da se odredi koeficijenat selektivnosti u njihovom dejstvu u odnosu na zdrave imunokompetentne ćelije. U cilju dobijanja uvida u mehanizam dejstva ispitivanih jedinjenja odrediće se tip ćelijske smrti koju indukuju ispitivani tetraoksani, kao i produkcija reaktivnih kiseoničnih vrsta u Hela ćelijama. Cilj 3D QSAR studije o antiproliferativoj aktivnosti trideset tri 1,2,4,5-tetraoksanska derivata prema Hela i Fem-x tumorskim ćelijskim linijama, je bio da se utvrdi koje su najvažnije farmakofore steroidnih tetraoksana koje utiču na potenciju ispitivanih jedinjenja prema HeLa i Fem-x tumorskim ćelijskim linijama. Materijal i metode: Citotoksično dejstvo tetraoksana DO-122 - DO-124 i DO-126 - DO-128, prema pet tumorskih ćelijskih linija je ispitivano standardnim MTT testom. U cilju određivanja tipa ćelijske smrti indukovane tretmanom ispitivanim tetraoksanima načinjena je morfološka analiza HeLa ćelija obojenih smešom akridin oranža i etidijum bromida. Analiza odr

Antiproliferative activity of 27 phenyl-substituted 4-aryl-4-oxo-2-butenoic acids (aroylacrylic acids) toward Human cervix carcinoma (HeLa), Human chronic myelogenous leukemia (K562) and Human colon tumor (LS174) cell lines in vitro are reported. Compounds are active toward all examined cell lines. The most active compounds bear two or three branched alkyl or cycloalkyl substituents on phenyl moiety having potencies in low micromolar ranges. One of most potent derivatives arrests the cell cycle at S phase in HeLa cells. The 3D QSAR study, using molecular interaction fields (MIF) and derived alignment independent descriptors (GRIND-2), rationalize the structural characteristics correlated with potency of compounds. Covalent chemistry, most possibly involved in the mode of action of reported compounds, was quantitatively accounted using frontier molecular orbitals. Pharmacophoric pattern of most potent compounds are used as a template for virtual screening, to find similar ones in database of compounds screened against DTP-NCI 60 tumor cell lines. Potency of obtained hits is well predicted. © 2011 Elsevier Masson SAS. All rights reserved.