Design,synthesis and biological evaluation of novel pyrazolo-oxothiazolidine derivatives as antiproliferative agents against human lung cancer cell line A549

An efficient, one-pot multicomponent reaction of novel pyrazolo-oxothiazolidine derivatives was achieved by condensation of 1-(benzofuran-2-yl)-3-(substituted-arylprop-2-en-1-ones, thiosemicarbazide and dialkyl acetylenedicarboxylates under the optimized reaction conditions. Synthesised compounds were evaluated for their antiproliferative activity against A549 human lung cancer cell line. Among all the tested compounds, 4a (IC₅₀ – 0.930?μg/mL), 4e (IC₅₀ – 1.207?μg/mL), 4f (IC₅₀ – 0.808?μg/mL), 4g (IC₅₀ – 1.078?μg/mL), 4h (IC₅₀ – 0.967?μg/mL) and 4j (IC₅₀ – 2.445?μg/mL) showed promising activity compared with standard drug Sorafenib (IC₅₀ – 3.779?μg/mL). Molecular docking studies indicated that compound 4f had the greatest affinity for catalytic site of receptors EGFR (PDB ID code: 1?M17) and VEGFR2 (PDB ID code: 4AGD, 4ASD). These novel pyrazolo-oxothiazolidine derivatives can be promising therapeutic agents for A549 human lung cancer cell line.     

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 PreliminaryIn Vitro Evaluation of Antimycobacterial Activity of New Pyrrolo[1,2-a]quinoxaline-carboxylic Acid Hydrazide Derivatives

New pyrrolo[1,2-a]quinoxaline-2- or -4-carboxylic acid hydrazide derivatives were synthesized from nitroaniline or 1,2-phenylenediamine, and evaluated in vitro for their antimycobacterial activity as part of a TAACF TB screening program. Two compounds 7c and 13 showed an interesting activity at 6.25?μg/mL against Mycobacterium tuberculosis H₃₇Rv, with a 94 and 100 percentage inhibition, respectively.     

Design,synthesis and molecular modeling of new 4-phenylcoumarin derivatives as tubulin polymerization inhibitors targeting MCF-7 breast cancer cells

A new set of 4-phenylcoumarin derivatives was designed and synthesized aiming to introduce new tubulin polymerization inhibitors as anti-breast cancer candidates. All the target compounds were evaluated for their cytotoxic effects against MCF-7 cell line, where compounds 2f, 3a, 3b, 3f, 7a and 7b, showed higher cytotoxic effect (IC₅₀?=?4.3–21.2?μg/mL) than the reference drug doxorubicin (IC₅₀?=?26.1?μg/mL), additionally, compounds 1 and 6b exhibited the same potency as doxorubicin (IC₅₀?=?25.2 and 28.0?μg/mL, respectively). The thiazolidinone derivatives 3a, 3b and 3f with potent and selective anticancer effects towards MCF-7 cells (IC₅₀?=?11.1, 16.7 and 21.2?μg/mL) were further assessed for tubulin polymerization inhibition effects which showed that the three compounds were potent tubulin polymerization suppressors with IC₅₀ values of 9.37, 2.89 and 6.13?μM, respectively, compared to the reference drug colchicine (IC₅₀?=?6.93?μM). The mechanistic effects on cell cycle progression and induction of apoptosis in MCF-7 cells were determined for compound 3a due to its potent and selective cytotoxic effects in addition to its promising tubulin polymerization inhibition potency. The results revealed that compound 3a induced cell cycle cessation at G2/M phase and accumulation of cells in pre-G1 phase and prevented its mitotic cycle, in addition to its activation of caspase-7 mediating apoptosis of MCF-7 cells. Molecular modeling studies for compounds 3a, 3b and 3f were carried out on tubulin crystallography, the results indicated that the compounds showed binding mode similar to the co-crystalized ligand; colchicine. Moreover, pharmacophore constructed models and docking studies revealed that thiazolidinone, acetamide and coumarin moieties are crucial for the activity. Molecular dynamics (MD) studies were carried out for the three compounds over 100?ps. MD results of compound 3a showed that it reached the stable state after 30?ps which was in agreement with the calculated potential and kinetic energy of compound 3a.     

Molecular properties prediction and synthesis of novel 1,3,4-oxadiazole analogues as potent antimicrobial and antitubercular agents

In the present investigation, a series of 1,5-dimethyl-2-phenyl-4-{[(5-aryl-1,3,4-oxadiazol-2-yl)methyl]amino}-1,2-dihydro-3H-pyrazol-3-one were subjected to molecular properties prediction, drug-likeness by Molinspiration (Molinspiration, 2008) and MolSoft (MolSoft, 2007) software, lipophilicity and solubility parameters using ALOGPS 2.1 program. The compounds followed the Lipinski ‘Rule of five’ were synthesized for antimicrobial and antitubercular screening as oral bioavailable drugs/leads. Maximum drug-likeness model score (0.95) was found for compound, 4a. All the synthesized compounds were characterized by IR, NMR and mass spectral analysis followed by antimicrobial and antimycobacterial screening. Among the title compounds, compound 4d showed pronounced activity against Mycobacterium tuberculosis H₃₇Rv and isoniazid resistant M. tuberculosis (INHR-TB) with minimum inhibitory concentrations (MICs) 0.78 μM and 1.52 μM, respectively. The compound, 4a showed maximum activity against all bacterial strains with MIC 4–8 μg/mL comparable to standard drug ciprofloxacin, while the compounds, 4e and 4k showed maximum antifungal activity with MIC 8–16 μg/mL less active than standard drug fluconazole.     

Synthesis,biological evaluations and computational studies of N-(3-(-2-(7-Chloroquinolin-2-yl)vinyl) benzylidene)anilines as fungal biofilm inhibitors

In the present investigation, new chloroquinoline derivatives bearing vinyl benzylidene aniline substituents at 2nd position were synthesized and screed for biofilm inhibitory, antifungal and antibacterial activity. The result of biofilm inhibition of C. albicans suggested that compounds 5j (IC₅₀ value?=?51.2?μM) and 5a (IC₅₀ value?=?66.2?μM) possess promising antibiofilm inhibition when compared with the standard antifungal drug fluconazole (IC₅₀?=?40.0?μM). Two compounds 5a (MIC?=?94.2?μg/mL) and 5f (MIC?=?98.8?μg/mL) also exhibited good antifungal activity comparable to standard drug fluconazole (MIC?=?50.0?μg/mL). The antibacterial screening against four strains of bacteria viz. E. coli, P. aeruginosa, B. subtilis, and S. aureus suggested their potential antibacterial activity and especially all the compounds except 5g were found more active than the standard drug ciprofloxacin against B. subtilis. To further gain insights into the possible mechanism of these compounds in biofilm inhibition through the agglutinin like protein (Als), molecular docking and molecular dynamics simulation studies were carried out. Molecular modeling studies suggested the clear role in inhibition of this protein and the resulting biofilm inhibitory activity.     

Synthesis of chiral pyrazolo[4,3-e][1,2,4]triazine sulfonamides with tyrosinase and urease inhibitory activity

A new series of sulfonamide derivatives of pyrazolo[4,3-e][1,2,4]triazine with chiral amino group has been synthesized and characterized. The compounds were tested for their tyrosinase and urease inhibitory activity. Evaluation of prepared derivatives demonstrated that compounds (8b) and (8j) are most potent mushroom tyrosinase inhibitors whereas all of the obtained compounds showed higher urease inhibitory activity than the standard thiourea. The compounds (8a), (8f) and (8i) exhibited excellent enzyme inhibitory activity with IC₅₀ 0.037, 0.044 and 0.042?μM, respectively, while IC₅₀ of thiourea is 20.9?μM.     

Synthesis,cyclooxygenase inhibition and anti-inflammatory evaluation of new 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivatives possessing methanesulphonyl pharmacophore

A new series of 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivatives 13a–p were synthesized via aldol condensation of 3/4-nitroacetophenones with appropriately substituted aldehydes followed by cyclization of the formed chalcones with 4-methanesulfonylphenylhydrazine hydrochloride. All the synthesized compounds were evaluated for their cyclooxygenase (COX) inhibition, anti-inflammatory activity and ulcerogenic liability. All compounds were more potent inhibitors for COX-2 than COX-1. While most compounds showed good anti-inflammatory activity, compounds 13d, 13f, 13k and 13o were the most potent derivatives (ED₅₀?=?66.5, 73.4, 79.8 and 70.5?μmol/kg, respectively) in comparison with celecoxib (ED₅₀?=?68.1?μmol/kg). Compounds 13d, 13f, 13k and 13o (ulcer index?=?3.89, 4.86, 4.96 and 3.92, respectively) were 4–6 folds less ulcerogenic than aspirin (ulcer index?=?22.75) and showed approximately ulceration effect similar to celecoxib (ulcer index?=?3.35). In addition, molecular docking studies were performed for compounds 13d, 13f, 13k and 13o inside COX-2 active site which showed acceptable binding interactions (affinity in kcal/mol ?2.1774, ?6.9498) in comparison with celecoxib (affinity in kcal/mol ?6.5330).     

Design,synthesis of novel pyranotriazolopyrimidines and evaluation of their anti-soybean lipoxygenase,anti-xanthine oxidase,and cytotoxic activities

The synthesis of 14-(aryl)-14H-naphto[2,1-b]pyrano[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine-2-yl) acetamidoximes 2a–e has been accomplished by reaction of 2-acetonitrile derivatives 1a–e with hydroxylamine. Cyclocondensation reaction of precursors 2a–e with some elctrophilic species such as ethylorthoformate, acetic anhydride, and methyl-acetoacetate provided the new oxadiazole derivatives 3a–e, 4a–e, and 5a–e, respectively. On the other hand, the reaction of precursors 2a–e with 2-chloropropanoyl chloride afforded the new acetimidamides 6a–e which evolve under reflux of toluene to the new oxadiazoles 7a–e. The synthetic compounds were screened for their anti-xanthine oxidase, anti-soybean lipoxygenase, and cytotoxic activities. Moderate to weak xanthine oxidase and soybean lipoxygenase inhibitions were obtained but significant cytotoxic activities were noted. The most cytotoxic activities were recorded mainly (i) 5a was the most active (IC_50?=_?4.0?μM) and selective against MCF-7 and (ii) 2a was cytotoxic against the four cell lines with selectivity for MCF-7 and OVCAR-3 (IC_50?=_?17 and 12?μM, respectively) while 2e is highly selective against OVCAR-3 (IC_50?=_?10?μM).     

Synthesis,antitumour activities and molecular docking of thiocarboxylic acid ester-based NSAID scaffolds: COX-2 inhibition and mechanistic studies

A new series of NSAID thioesters were synthesized and evaluated for their in vitro antitumor effects against a panel of four human tumor cell lines, namely: HepG2, MCF-7, HCT-116 and Caco-2, using the MTT assay. Compared to the reference drugs 5-FU, afatinib and celecoxib, compounds 2b, 3b, 6a, 7a, 7b and 8a showed potent broad-spectrum antitumor activity against the selected tumour cell lines. Accordingly, these compounds were selected for mechanistic studies about COX inhibition and kinase assays. In vitro COX-1/COX-2 enzyme inhibition assay results indicated that compounds 2b, 3b, 6a, 7a, 7b, 8a and 8?b selectively inhibited the COX-2 enzyme (IC₅₀?=?～0.20–0.69?μM), with SI values of (>72.5–250) compared with celecoxib (IC₅₀?=?0.16?μM, COX-2 SI:?>?312.5); however, all the tested compounds did not inhibit the COX-1 enzyme (IC₅₀?>?50?μM). On the other hand, EGFR, HER2, HER4 and cSrc kinase inhibition assays were evaluated at a 10?μM concentration. The selected candidates displayed limited activities against the various tested kinases; the compounds 2a, 3b, 6a, 7a, 7b and 8a showed no activity to weak activity (% inhibition?=?～0–10%). The molecular docking study revealed the importance of the thioester moiety for the interaction of the drugs with the amino acids in the active sites of COX-2. The aforementioned results indicated that thioester based on NSAID scaffolds derivatives may serve as new antitumor compounds.     

Synthesis and Antileishmanial Activity of 3-Imidazolylalkylindoles. Part I

The present study was designed to investigate conazoles as new antileishmanial agents. Several 3-imidazolylalkylindoles were prepared under mild reaction conditions and pharmacomodulation at N1 and C5 of the indole ring and at the level of the alkyl chain (R) was carried out starting from the corresponding 3-formylindoles 7–10. All target imidazolyl compounds 38–52 were evaluated in vitro against Leishmania mexicana promastigotes; ketoconazole, amphotericin B and meglumine antimoniate were used as references. Eight out of fifteen compounds (40, 43, 44, 47, 48, 50, 51 and 52) exerted similar activity to ketoconazole, with IC₅₀ values in the range of 2.10–3.30?μg/mL. However the most potent compound, 1-(2-bromobenzyl)-3-(1H-imidazol-1-ylmethyl)-1H-indole (38), exhibited IC₅₀ value (0.011±0.003?μg/mL) 270-fold lower than that of ketoconazole. Four compounds (38, 43, 50 and 52) were also tested against intracellular amastigotes of L. mexicana; compound 38 exhibited the highest activity with an IC₅₀ value of 0.018±0.004?μg/mL.     

Synthesis of new pyridothienopyrimidinone derivatives as Pim-1 inhibitors

Four series of pyridothienopyrimidin-4-one derivatives were designed and prepared to improve the pim-1 inhibitory activity of the previously reported thieno[2,3-b]pyridines. Significant improvement in the pim-1 inhibition and cytotoxic activity was achieved using structure rigidification strategy via ring closure. Six compounds (6c, 7a, 7c, 7d, 8b and 9) showed highly potent pim-1 inhibitory activity with IC₅₀ of 4.62, 1.18, 1.38, 1.97, 8.83 and 4.18?μM, respectively. Four other compounds (6b, 6d, 7b and 8a) showed moderate pim-1 inhibition. The most active compounds were tested for their cytotoxic activity on three cell lines [MCF7, HCT116 and PC3]. Compounds 7a [the 2-(2-chlorophenyl)-2,3-dihydro derivative] and 7d [the 2-(2-(trifluoromethyl)-phenyl)-2,3-dihydro derivative] displayed the most potent cytotoxic effect on the three cell lines tested consistent with their highest estimated pim-1 IC₅₀ values.     

Synthesis and biological evaluation of 2-styrylquinolines as antitumour agents and EGFR kinase inhibitors: molecular docking study

A new series of 4,6-disubstituted 2-(4-(dimethylamino)styryl)quinoline 4a,b–9a,b was synthesized by the reaction of 2-(4-(dimethylamino)styryl)-6-substituted quinoline-4-carboxylic acids 3a,b with thiosemicarbazide, p-hydroxybenzaldehyde, ethylcyanoacetate, and 2,4-pentandione. In addition, the antitumour activity of all synthesized compounds 3a,b–9a,b was studied via MTT assay against two cancer cell lines (HepG2 and HCT116). Furthermore, epidermal growth factor receptor (EGFR) inhibition, using the most potent antitumour compounds, 3a, 3b, 4a, 4b, and 8a, was evaluated. The interpretation of the results showed clearly that the derivatives 3a, 4a, and 4b exhibited the highest antitumour activities against the tested cell lines HepG2 and HCT116 with IC₅₀ range of 7.7–14.2?µg/ml, in comparison with the reference drugs 5-fluorouracil (IC₅₀?=?7.9 and 5.3?µg/ml, respectively) and afatinib (IC₅₀?=?5.4 and 11.4?µg/ml, respectively). In vitro EGFR screening showed that compounds 3a, 3b, 4a, 4b, and 8a exhibited moderate inhibition towards EGFR with IC₅₀ values at micromolar levels (IC₅₀ range of 16.01–1.11?µM) compared with the reference drugs sorafenib (IC₅₀ =?1.14?µM) and erlotinib (IC₅₀ =?0.1?µM). Molecular docking was performed to study the mode of interaction of compounds 3a and 4b with EGFR kinase.     

Synthesis and biological evaluation of novel 3-substituted amino-4-hydroxylcoumarin derivatives as chitin synthase inhibitors and antifungal agents

A series of novel 3-substituted amino-4-hydroxycoumarin derivatives have been designed and synthesized as chitin synthase (CHS) inhibitors. All the synthesized compounds have been screened for their CHS inhibition activity and antimicrobial activity in vitro. The enzymatic assay indicated that most of the compounds have good inhibitory activity against CHS, in which compound 6o with IC₅₀ of 0.10?mmol/L had stronger activity than that of polyoxins B, which acts as control drug with IC₅₀ of 0.18?mmol/L. As far as the antifungal activity is concerned, most of the compounds possessed moderate to excellent activity against some representative pathogenic fungi. Especially, compound 6b was found to be the most potent agent against Cryptococcus neoformans with minimal inhibitory concentration (MIC) of 4?μg/mL. Moreover, the results of antibacterial screening showed that these compounds have negligible actions to some tested bacteria. Therefore, these compounds would be promising to develop selective antifungal agents.     

Synthesis and antitumor activity of tetrahydrocarbazole hybridized with dithioate derivatives

Abstract

The present study reported the synthesis of tetrahydrocarbazoles hybridized with dithioate derivatives. Three series were synthesized namely alkyl dithiocarbonates (4a–d), heterocyclic dithiocarbamates (6a–g) and dialkyl dithiocarbamate (7). The synthesized compounds were tested in vitro on human breast adenocarcinoma cell line (MCF7) and the human colon tumor cell line (HCT116). Most of the synthesized compounds exploited potent antitumor activity, especially compound 6f [4-chlorophenylpiperazine derivative], which showed cytotoxic activity against MCF7 superior to doxorubicin with IC₅₀ value of 7.24?nM/mL.     

Design,synthesis, antimicrobial evaluation and molecular docking studies of some new 2,3-dihydrothiazoles and 4-thiazolidinones containing sulfisoxazole

Microbial resistance to the available drugs poses a serious threat in modern medicine. We report the design, synthesis and in vitro antimicrobial evaluation of new functionalized 2,3-dihydrothiazoles and 4-thiazolidinones tagged with sulfisoxazole moiety. Compound 8d was most active against Bacillis subtilis (MIC, 0.007?µg/mL). Moreover, compounds 7c–d and 8c displayed significant activities against B. subtilis and Streptococcus pneumoniae (MIC, 0.03–0.06?µg/mL and 0.06–0.12?µg/mL versus ampicillin 0.24?µg/mL and 0.12?µg/mL; respectively). Compounds 7a and 7c–d were highly potent against Escherichia coli (MIC, 0.49–0.98?µg/mL versus gentamycin 1.95?µg/mL). On the other hand, compounds 7e and 9c were fourfolds more active than amphotericin B against Syncephalastrum racemosum. Molecular docking studies showed that the synthesized compounds could act as inhibitors for the dihydropteroate synthase enzyme (DHPS). This study is a platform for the future design of more potent antimicrobial agents.     

Synthesis and evaluation of sulfonamide-bearing thiazole as carbonic anhydrase isoforms hCA I and hCA II

Sulfonamide-bearing thiazole compounds were synthesized and their inhibitory effects on the activity of purified human carbonic anhydrase I and II were evaluated. Human carbonic anhydrase isoenzymes (hCA-I and hCA-II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of the 12 synthesized sulfonamide (5a–l) on the hydratase and esterase activities of these isoenzymes (hCA-I and hCA-II) were studied in vitro. In relation to these activities, the inhibition equilibrium constants (Ki) were determined. The results showed that all the synthesized compounds inhibited the CA isoenzyme activity. Among them 5b was found to be the most active (IC_50?=_?0.35?μM; Ki: 0.33?μM) for hCA I and hCA II.     

Metabolite profile and in vitro activities of Phagnalon saxatile (L.) Cass. relevant to treatment of Alzheimer’s disease

The present study describes for the first time the in vitro properties (inhibition of NO production and anticholinesterase) of Phagnalon saxatile (L.) Cass. (Asteraceae). The methanolic extract showed antioxidant activity that was measured by DPPH assay and β-carotene bleaching test. The same extract inhibited NO production in the murine monocytic macrophage cell line RAW 264.7. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition was assessed by modifications of Ellman’s method. Purification of the MeOH extract of P. saxatile allowed the isolation of phenolic compounds. Among them, the compounds that most effectively inhibited lipopolysaccharide-induced NO production were caffeic acid and methylchlorogenic acid, with IC₅₀ values of 7?μg/mL and 12?μg/mL, respectively. Luteolin and 3,5-dicaffeoylquinic acid exhibited the most promising activity against AChE with an IC₅₀ of 25.2 and 54.5?μg/mL, respectively, while caffeic acid and luteolin exhibited higher activity against BChE with an IC₅₀ of 32.2 and 37.2?μg/mL, respectively.     

Synthesis and in vitro Biological Evaluation of Novel Thymidine Analogs Containing 1H-1,2,3-Triazolyl, 1H-Tetrazolyl,and 2H-Tetrazolyl Fragments

Abstract

3′-Azidothymidine (AZT) reacts with 1-propargyl-5-R-1H- and 2-propargyl-5-R-2H-tetrazoles (R?=?H, Me, CH₂COOEt, CH₂CON(CH₃)₂, Ph, 2-CH₃-C₆H₄, or 4-NO₂-C₆H₄) via the Cu(I)-catalyzed asymmetric [3?+?2] cycloaddition to give 3′-modified thymidine analogs incorporating 1H-1,2,3-triazolyl, 1H-, and 2H-tetrazolyl fragments in 41–76% yield. The structures of the obtained compounds have been elucidated by means of HRESI⁺-MS, ¹H and ¹³ Ostrovskii, V. A.; Popova, E. A.; Trifonov, R. E. Developments in Tetrazole Chemistry (2009–16). Advances in heterocyclic chemistry. 2017, 123, 2–62.[Web of Science ®] , [Google Scholar]C{¹H} NMR, and single crystal X-ray diffraction {for 3′-[4-(1H-5-N,N-dimethylaminocarbonylmethyltetrazol-1-yl)-1H-1,2,3-triazol-1-yl]thymidine 10d}. In vitro biological evaluation of the prepared compounds has been performed; they have exhibited low activity against phenotypic HIV-1_899A. Moderate anti-influenza activity against influenza virus A/Puerto Rico/8/34 (H1N1) strain has been observed in the cases of 3′-(4-(1H-tetrazol-1-ylmethyl)-1H-1,2,3-triazol-1-yl)thymidine 10a (IC₅₀ 39.6?μg/mL), 3′-(4-(2H-5-ethoxycarbonyltetrazol-2-ylmethyl)-1H-1,2,3-triazol-1-yl)thymidine 11c (IC₅₀ 31.6?μg/mL), and 3′-(4-(2H-5-(4-nitrophenyl)-tetrazol-2-ylmethyl)-1H-1,2,3-triazol-1-yl)thymidine 11g (IC₅₀ 46.4?μg/mL). The tested compounds possess very low cytotoxicity towards MDCK and MT4 cells as well as tumor human cervical carcinoma HeLa and promyelocytic leukemia HL-60 cells.     

Cancer stem cells CD133 inhibition and cytotoxicity of certain 3-phenylthiazolo[3,2-a]benzimidazoles: design,direct synthesis,crystal study and in vitro biological evaluation

Cancer stem cells (CSCs) have been objects of intensive study since their identification in 1994. Adopting a structural rigidification approach, a novel series of 3-phenylthiazolo[3,2-a]benzimidazoles 4a–d was designed and synthesised, in an attempt to develop potent anticancer agent that can target the bulk of tumour cells and CSCs. The anti-proliferative activity of the synthesised compounds was evaluated against two cell lines, namely; colon cancer HT-29 and triple negative breast cancer MDA-MB-468 cell lines. Also, their inhibitory activity against the cell surface expression of CD133 was examined. In particular, compound 4b emerged as a promising hit molecule as it manifested good antineoplastic potency against both tested cell lines (IC₅₀?=?9 and 12?μM, respectively), beside its ability to inhibit the cell surface expression of CD133 by 50% suggesting a promising potential of effectively controlling the tumour by eradicating the tumour bulk and inhibiting the proliferation of the CSCs. Moreover, compounds 4a and 4c showed moderate activity against HT-29 (IC₅₀?=?21 and 29?μM, respectively) and MDA-MB-468 (IC₅₀?=?23 and 24?μM, respectively) cell lines, while they inhibited the CD133 expression by 14% and 48%, respectively. Finally, a single crystal X-ray diffraction was recorded for compound 4d.