Quinazolin‐4(3H)‐one‐Based Hydroxamic Acids: Design,Synthesis and Evaluation of Histone Deacetylase Inhibitory Effects and Cytotoxicity

The present article describes the synthesis and biological activity of various series of novel hydroxamic acids incorporating quinazolin‐4(3H)‐ones as novel small molecules targeting histone deacetylases. Biological evaluation showed that these hydroxamic acids were potently cytotoxic against three human cancer cell lines (SW620, colon; PC‐3, prostate; NCI?H23, lung). Most compounds displayed superior cytotoxicity than SAHA (suberoylanilide hydroxamic acid, Vorinostat) in term of cytotoxicity. Especially, N‐hydroxy‐7‐(7‐methyl‐4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5b ) and N‐hydroxy‐7‐(6‐methyl‐4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5c ) (IC₅₀ values, 0.10–0.16 μm ) were found to be approximately 30‐fold more cytotoxic than SAHA (IC₅₀ values of 3.29–3.67 μm ). N‐Hydroxy‐7‐(4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5a ; IC₅₀ values of 0.21–0.38 μm ) was approximately 10‐ to 15‐fold more potent than SAHA in cytotoxicity assay. These compounds also showed comparable HDAC inhibition potency with IC₅₀ values in sub‐micromolar ranges. Molecular docking experiments indicated that most compounds, as represented by 5b and 5c , strictly bound to HDAC2 at the active binding site with binding affinities much higher than that of SAHA.     

New Acetohydrazides Incorporating 2‐Oxoindoline and 4‐Oxoquinazoline: Synthesis and Evaluation of Cytotoxicity and Caspase Activation Activity

In our search for new small molecules activating procaspase‐3, we have designed and synthesized a series of new acetohydrazides incorporating both 2‐oxoindoline and 4‐oxoquinazoline scaffolds. Biological evaluation showed that a number of these acetohydrazides were comparably or even more cytotoxic against three human cancer cell lines (SW620, colon cancer; PC‐3, prostate cancer; NCI?H23, lung cancer) in comparison to PAC‐1, a first procaspase‐3 activating compound, which was used as a positive control. One of those new compounds, 2‐(6‐chloro‐4‐oxoquinazolin‐3(4H)‐yl)‐N′‐[(3Z)‐5‐methyl‐2‐oxo‐1,2‐dihydro‐3H‐indol‐3‐ylidene]acetohydrazide activated the caspase‐3 activity in U937 human lymphoma cells by 5‐fold higher than the untreated control. Three of the new compounds significantly induced necrosis and apoptosis in U937 cells.     

N‐[2‐[(3‐Chlorophenyl)amino]‐phenyl]‐3‐(difluoromethyl)‐1‐methyl‐1H‐pyrazole‐4‐carboxamide: Synthesis,Crystal Structure,Molecular Docking and Biological Activities

In continuation of our previous research on the development of novel pyrazole‐4‐carboxamide with potential antifungal activity, compound SCU2028 , namely N‐[2‐[(3‐chlorophenyl)amino]phenyl]‐3‐(difluoromethyl)‐1‐methyl‐1H‐pyrazole‐4‐carboxamide, was synthesized by new method, structurally characterized by IR, HR‐ESI‐MS, ¹H‐ and ¹³C‐NMR spectra and further identified by single‐crystal X‐ray diffraction. In pot tests, compound SCU2028 showed good in vivo antifungal activity against Rhizoctonia solani (R. solani) and IC₅₀ value of it was 7.48 mg L^?1. In field trials, control efficacy of compound SCU2028 at 200 g.a.i. ha^?1 was 42.30 % on the 7^th day after the first spraying and 68.10 % on the 14^th day after the second spraying, only slightly lower than that of thifluzamide (57.20 % and 71.40 %, respectively). Further in vitro inhibitory activity showed inhibitory ability of compound SCU2028 was 45‐fold higher than that of bixafen and molecular docking of compound SCU2028 to SDH predicted its binding orientation in the active site of the target protein SDH. These results suggested that compound SCU2028 was a potential fungicide for control of rice sheath blight.     

Lewis acid catalysed methylation of N‐(9H‐fluoren‐9‐yl)methanesulfonyl (Fms) protected lipophilic α‐amino acid methyl esters

This work reports an efficient Lewis acid catalysed N‐methylation procedure of lipophilic α‐amino acid methyl esters in solution phase. The developed methodology involves the use of the reagent system AlCl₃/diazomethane as methylating agent and α‐amino acid methyl esters protected on the amino function with the (9H‐fluoren‐9‐yl)methanesulfonyl (Fms) group. The removal of Fms protecting group is achieved under the same conditions to those used for Fmoc removal. Thus the Fms group can be interchangeable with the Fmoc group in the synthesis of N‐methylated peptides using standard Fmoc‐based strategies. Finally, the absence of racemization during the methylation reaction and the removal of Fms group were demonstrated by synthesising a pair of diastereomeric dipeptides. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.     

Synthesis of the N‐methyl Derivatives of 2‐Aminothiazol‐4(5H)‐one and Their Interactions with 11βHSD1‐Molecular Modeling and in Vitro Studies

11β‐Hydroxysteroid dehydrogenase type 1 (11β‐HSD1) is an enzyme that affects the body's cortisol levels. The inhibition of its activity can be used in the treatment of Cushing's syndrome, metabolic syndrome and type 2 diabetes. In this study, we synthesized new derivatives of 2‐(methylamino)thiazol‐4(5H)‐one and tested their activity towards inhibition of 11β‐HSD1 and its isoform – 11β‐HSD2. The results were compared with the previously tested allyl derivatives. We found out that methyl derivatives are weaker inhibitors of 11β‐HSD1 in comparison to their allyl analogs. Due to significant differences in the activity of the compounds, molecular modeling was performed, which was aimed at comparing the interactions between 11β‐HSD1 and ligands differing by substituent at the amine group (allyl vs. methyl). Modeling showed that the absence of the allyl group can lead to the rotation of whole ligand molecule which affects its interaction with the enzyme.     

Synthesis of 3‐Methylidene‐1‐tosyl‐2,3‐dihydroquinolin‐4(1H)‐ones as Potent Cytotoxic Agents

An efficient synthetic strategy to 3‐methylidene‐2,3‐dihydroquinolin‐4(1H)‐ones variously substituted in position 2 has been developed. The title compounds were synthesized in the reaction sequence involving reaction of diethyl methylphosphonate with methyl 2‐(tosylamino)benzoate, condensation of thus formed diethyl 2‐oxo‐2‐(2‐N‐tosylphenyl)ethylphosphonate with various aldehydes followed by successful application of the obtained 3‐(diethoxyphosphoryl)‐1,2‐dihydroquinolin‐4‐ols as Horner–Wadsworth–Emmons reagents for the olefination of formaldehyde. Also, enantioselective approach to the target compounds has been evaluated using 3‐dimenthoxyphosphoryl group as a chiral auxiliary. Single X‐ray crystal analysis of (2S)‐3‐(dimenthoxyphosphoryl)‐2‐phenyl‐1‐tosyldihydroquinolin‐4‐ol revealed the presence of strong resonance‐assisted hydrogen bond (RAHB). The obtained 3‐methylidene‐2,3‐dihydroquinolin‐4(1H)‐ones were then tested for their cytotoxic activity against two leukemia cell lines NALM‐6 and HL‐60 and a breast cancer MCF‐7 cell line. All compounds showed very high cytotoxic activity with the IC₅₀ values mostly below 1 μm in all three cancer cell lines. The selected analogs were also tested on human umbilical vein endothelial cells (HUVEC) and on human mammary gland/breast cells (MCF‐10A) to evaluate their influence on normal cells. Since one of the most serious problems in cancer chemotherapy is the development of drug resistance, the mRNA levels and activity of ABCB1 transporter considered to be the most important factor engaged in drug resistance, were evaluated in MCF‐7 cells treated with two selected analogs. Both compounds were strong ABCB1 transporter inhibitors that could prevent efflux of anticancer drugs from cancer cells.     

Synthesis of 6‐[4‐(4‐Propoxyphenyl)piperazin‐1‐yl]‐9H‐purine Derivatives as Antimycobacterial and Antifungal Agents: In Vitro Evaluation and In Silico Study

A series of novel alkyl substituted purines were synthesized. 6‐[4‐(4‐Propoxyphenyl)piperazin‐1‐yl]‐9H‐purine was used as the key starting material, which was synthesized via a multistep protocol and finally subjected for N‐alkylation with various alkyl halides with an aim to get prospective antimicrobial agents. The structures of the novel compounds were established by substantiating them through spectral techniques like ¹H‐NMR, ¹³C‐NMR, FT‐IR and EI‐MS. They were explored for antitubercular activity against Mycobacterium tuberculosis H37RV. Furthermore, they were checked for their antimicrobial activity concerning bacterial and fungal strains. The title compounds exhibited considerable antimicrobial activity without any significant toxicity. In silico studies depicted their good binding profile against Mycobacterium tuberculosis enoyl reductase (InhA; PDB ID: 4TZK) and Candida albicans dihydrofolate reductase (PDB ID: 1AI9). The title compounds obeyed Lipinski's parameters and have exhibited good drug‐like properties.     

Design,synthesis, and anti-cancer evaluation of new pyrido[2,3-d]pyrimidin-4(3H)-one derivatives as potential EGFRWT and EGFRT790M inhibitors and apoptosis inducers

A new series of pyrido[2,3-d]pyrimidin-4(3H)-one derivatives having the essential pharmacophoric features of EGFR inhibitors has been designed and synthesised. Cell viability screening was performed for these compounds against A-549, PC-3, HCT-116, and MCF-7 cell lines at a dose of 100 μM. The highest active derivatives (8a, 8 b, 8d, 9a, and 12b) were selected for IC₅₀ screening. Compounds 8a, 8 b, and 9a showed the highest cytotoxic activities and were further investigated for wild EGFR^WT and mutant EGFR^T790M inhibitory activities. Compound 8a showed the highest inhibitory activities against EGFR^WT and EGFR^T790M with IC₅₀ values of 0.099 and 0.123 µM, respectively. In addition, it arrested the cell cycle at pre-G1 phase and induced a significant apoptotic effect in PC-3 cells. Furthermore, compound 8a induced a 5.3-fold increase in the level of caspase-3 in PC-3 cells. Finally, docking studies were carried out to examine the binding mode of the synthesised compounds against both EGFR^WT and EGFR^T790M.     

Exploring MDR‐TB Inhibitory Potential of 4‐Aminoquinazolines as Mycobacterium tuberculosis N‐Acetylglucosamine‐1‐Phosphate Uridyltransferase (GlmUMTB) Inhibitors

Drug resistance tuberculosis is one of the challenging tasks that dictates the desperate need for the development of new antitubercular agents which operate via novel modes of action. Here, we are reporting on 4‐aminoquinazolines as M. tuberculosis N‐acetylglucosamine‐1‐phosphate uridyltransferase (GlmU^MTB) inhibitors to overcome the problem of the MDR‐TB. Amongst the synthesized compounds, two of them were observed to be the effective compounds of the series (IC₅₀=6.4 μM (H37Rv), MIC=25 μM (MDR‐TB) and IC₅₀=2.9 μM (H37Rv), MIC=6.25 μM (MDR‐TB), respectively).     

Synthesis and application of Nα‐Fmoc‐Nπ‐4‐methoxybenzyloxymethylhistidine in solid phase peptide synthesis

The 4‐methoxybenzyloxymethyl (MBom) group was introduced at the N^π‐position of the histidine (His) residue by using a regioselective procedure, and its utility was examined under standard conditions used for the conventional and the microwave (MW)‐assisted solid phase peptide synthesis (SPPS) with 9‐fluorenylmethyoxycarbonyl (Fmoc) chemistry. The N^π‐MBom group fulfilling the requirements for the Fmoc strategy was found to prevent side‐chain‐induced racemization during incorporation of the His residue even in the case of MW‐assisted SPPS performed at a high temperature. In particular, the MBom group proved to be a suitable protecting group for the convergent synthesis because it remains attached to the imidazole ring during detachment of the protected His‐containing peptide segments from acid‐sensitive linkers by treatment with a weak acid such as 1% trifluoroacetic acid in dichloromethane. We also demonstrated the facile synthesis of Fmoc‐His(π‐MBom)‐OH with the aid of purification procedure by crystallization to effectively remove the undesired τ‐isomer without resorting to silica gel column chromatography. This means that the present synthetic procedure can be used for large‐scale production without any obstacles. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.     

Novel (E)-3-(3-Oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides as Histone Deacetylase Inhibitors: Design,Synthesis and Bioevaluation

Herein, we report the design, synthesis and evaluation of novel (E)-3-(3-oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides ( 4 a – i , 7 a – g ) targeting histone deacetylases. Three human cancer cell lines were used to test the cytotoxicity of the synthesized compounds (SW620, colon; PC-3, prostate; NCI−H23, lung cancer); inhibitory activity towards HDAC; anticancer activity; as well as their impact on the cell cycle and apoptosis. As a result, compounds 4 a – i bearing the alkyl substituents seemed to be less potent than the benzyl-containing compounds 7 a – g in all biological assays. Compounds 7 e – f were found to be the most active HDAC inhibitors with IC₅₀ of 1.498±0.020 μM and 1.794±0.159 μM, respectively. In terms of cytotoxicity and anticancer assay, 7 e and 7 f also showed good activity with IC₅₀ values in the micromolar range. In addition, the cell cycle and apoptosis of SW620 were affected by compound 7 f in almost a similar manner to that of reference compound SAHA. Docking assays were carried out for analysis the binding mode and selectivity of this compound toward 8 HDAC isoforms. Overall, our data confirmed that the inhibition of HDAC plays a pivotal role in their anticancer activity.     

Synthesis,biological evaluation and docking studies of 2,3-dihydroquinazolin-4(1H)-one derivatives as inhibitors of cholinesterases

In search of potent inhibitors of cholinesterases, we have synthesized and evaluate a number of 2,3-dihydroquinazolin-4(1H)-one derivatives. The synthetic approach provided an efficient synthesis of the target molecules with excellent yield. All the tested compounds showed activity against both the enzymes in micromolar range. In many case, the inhibition of both enzymes are higher than or comparable to the standard drug galatamine. With the selectivity index of 2.3 for AChE, compound 5f can be considered as a potential lead compound with a feature of dual AChE/BChE inhibition with IC₅₀ = 1.6 ± 0.10 μM (AChE) and 3.7 ± 0.18 μM (BChE). Binding modes of the synthesized compounds were explored by using GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. The computed binding modes of these compounds in the active site of AChE and BChE provide an insight into the mechanism of inhibition of these two enzyme.     

In Vitro and In Vivo Evaluation of N‐{2‐[4‐(3‐Cyanopyridin‐2‐yl)piperazin‐1‐yl]ethyl}‐3‐[11C]methoxybenz­amide,a Positron Emission Tomography (PET) Radioligand for Dopamine D4 Receptors,in Rodents

The D₄ dopamine receptor belongs to the D₂‐like family of dopamine receptors, and its exact regional distribution in the central nervous system is still a matter of considerable debate. The availability of a selective radioligand for the D₄ receptor with suitable properties for positron emission tomography (PET) would help resolve issues of D₄ receptor localization in the brain, and the presumed diurnal change of expressed protein in the eye and pineal gland. We report here on in vitro and in vivo characteristics of the high‐affinity D₄ receptor‐selective ligand N‐{2‐[4‐(3‐cyanopyridin‐2‐yl)piperazin‐1‐yl]ethyl}‐3‐[¹¹C]methoxybenzamide ([¹¹C] 2 ) in rat. The results provide new insights on the in vitro properties that a brain PET dopamine D₄ radioligand should possess in order to have improved in vivo utility in rodents.     

Synthesis and chemiluminescence of copolymers of 5-amino-8-vinyl-phthalazine-1, 4(2H,3H)-dione with methyl methacrylate or styrene,and of α, ω-bis[5-amino-phthalazine-1,4 (2H,3H)-dion-]8-yl alkanes [=α, ω-bis(6-luminyl) alkanes]: Investigations on an intramolecular ‘distance effect’

Oligomers of 5-amino-8-vinyl-phthalazine-1,4(2H,3H)-dione exhibit about 0.05% of the chemiluminescence quantum yield of the corresponding ‘monomer unit’, i.e. 5-amino-8-ethyl-phthalazine-1,4(2H,3H)-dione which has a similar quantum yield to luminol. The quantum yields of copolymers of 5-amino-8-vinyl-phthalazine-1,4(2H,3H)-dione (1a) with methyl methacrylate or with styrene increase up to 1000-fold, relative to the quantum yield of oligomers of (1a). Thus the monomer units of methyl methacrylate or styrene appear to act as ‘spacers’ between the lumigenic groups. α,ω-Bis[(5-amino-phthalazine-1,4(2H,3H)-dion-)8-yl] alkanes show an analogue ‘distance’ effect: the chemiluminescence quantum yield increases with increasing alkane chain length. As the fluorescence of the corresponding amino phthalates (which are intermediates in the synthesis of the phthalazine diones) is only slightly influenced by the distance between the lumigenic groups it is suggested that a mainly chemical ‘distance effect’ is working here: the smaller the intramolecular distance between the hydrazide groups the more inhibition exists in respect of the oxidative reaction producing the luminol-type chemiluminescence.     

Plasma and liver proteomic analysis of 3Z‐3‐[(1H‐pyrrol‐2‐yl)‐methylidene]‐1‐(1‐piperidinylmethyl)‐1,3‐2H‐indol‐2‐one‐induced hepatotoxicity in Wistar rats

3Z‐3‐[(1H‐pyrrol‐2‐yl)‐methylidene]‐1‐(1‐piperidinylmethyl)‐1,3‐2H‐indol‐2‐one (Z24), a synthetic anti‐angiogenic compound, inhibits the growth and metastasis of certain tumors. Previous works have shown that Z24 induces hepatotoxicity in rodents. We examined the hepatotoxic mechanism of Z24 at the protein level and looked for potential biomarkers. We used 2‐DE and MALDI‐TOF/TOF MS to analyze alternatively expressed proteins in rat liver and plasma after Z24 administration. We also examined apoptosis in rat liver and measured levels of intramitochondrial ROS and NAD(P)H redox in liver cells. We found that 22 nonredundant proteins in the liver and 11 in the plasma were differentially expressed. These proteins were involved in several important metabolic pathways, including carbohydrate, lipid, amino acid, and energy metabolism, biotransformation, apoptosis, etc. Apoptosis in rat liver was confirmed with the terminal deoxynucleotidyl transferase dUTP‐nick end labeling assay. In mitochondria, Z24 increased the ROS and decreased the NAD(P)H levels. Thus, inhibition of carbohydrate aerobic oxidation, fatty acid β‐oxidation, and oxidative phosphorylation is a potential mechanism of Z24‐induced hepatotoxicity, resulting in mitochondrial dysfunction and apoptosis‐mediated cell death. In addition, fetub protein and argininosuccinate synthase in plasma may be potential biomarkers of Z24‐induced hepatotoxicity.     

Synthesis and optical resolution of 1‐[(3‐carboxy‐1,1′‐biphenyl)‐2‐yl]‐1H‐pyrrole‐2‐carboxylic acid

Site selective mono‐ and dimetalation methods have been developed for the functionalization of 1‐[(1,1′‐biphenyl)‐2‐yl]‐1H‐pyrrole. Optical resolution of the prepared 1‐[(3‐carboxy‐1,1′‐biphenyl)‐2‐yl]pyrrole‐2‐carboxylic acid provided new atropisomeric 1‐arylpyrrole derivatives. The absolute configuration of the pure dicarboxylic acid enantiomers was determined by single crystal X‐ray diffraction and CD spectroscopy. Chirality 2009. © 2009 Wiley‐Liss, Inc.     

Discovery and synthesis of 2-amino-1-methyl-1H-imidazol-4(5H)-ones as GPCR ligands; an approach to develop breast cancer drugs via GPCR associated PAR1 and PI3Kinase inhibition mechanism

Efforts were taken to synthesis and characterize 2-amino-1-methyl-1H-imidazole-4(5H)-one derivatives (4a-u) through a four-step reaction. The achieved compounds in remarkable yield have characterized through standard analytical techniques such as FTIR, LC-MS, NMR, HRMS, and elemental analysis. Present study mainly aimed to evaluate 4a-u as G protein-coupled receptors (GPCR). In the mechanism, stimulation of phosphoinositide 3-kinase (PI3K) and Akt (protein kinase B) is a general reaction activated by a series of membrane-bound receptors such as GPCR. Protease-activated receptor-1 (PAR1) is a subfamily of related GPCR, which triggered by the division of fragment of its extracellular domain. Therefore, molecular docking is done to ensure the inhibition of PAR1 and PI3Kinase. PI3Kinase is a chief enzyme in the development of breast cancer via the Akt/mTOR pathway. Thus, in vitro PI3Kinase inhibition and anti-breast cancer studies has also done to screen medicinally important compounds among (4a-u). Based on the best binding affinity, in vitro relative % activity and IC₅₀ values, compounds 4a, 4g, 4i, 4n, and 4u were screened for further preclinical studies in animal model evaluations.     

Synthesis and Biological Evaluation of Novel 1‐(4‐(Hydroxy(1‐oxo‐1,3‐dihydro‐2H‐inden‐2‐ylidene)methyl)phenyl)‐3‐phenylurea Derivatives

A series of novel phenylurea containing 2‐benzoylindan‐1‐one derivatives 3a  –  3j were synthesized from the reaction of phenylurea‐substituted acetophenones 1a  –  1j with phthalaldehyde 2 under mild reaction conditions in good yields. All synthesized compounds were characterized by spectroscopic methods. The obtained compounds ( 3a  –  3j ) were evaluated for anticancer activity against HeLa and C6 cell lines. Antiproliferative activity was determined by the BrdU proliferation ELISA assay, 3f and 3g were found to be most active compounds. The compounds were also screened for antimicrobial activity and all compounds showed remarkable activity against used microorganisms.     

Synthesis and structure of a new trinuclear nickel(II) complex bridged by N‐[3‐(Dimethylamino)propyl]‐N′‐(2‐hydroxyphenyl)oxamido: in vitro anticancer activities,and reactivities toward DNA and protein

A new trinickel(II) complex bridged by N‐[3‐(dimethylamino)propyl]‐ N ′‐(2‐hydroxylphenyl)oxamido (H₃pdmapo), namely [Ni₃(pdmapo)₂(H₂O)₂]?4CH₃OH, was synthesized and characterized by X‐ray single‐crystal diffraction and other methods. In the molecule, two symmetric cis‐ pdmapo^3? mononickel(II) complexes as a “complex ligand” using the carbonyl oxygen atoms coordinate to the center nickel(II) ion situated on an inversion point. The Ni···Ni distance through the oxamido bridge is 5.2624(4) Å. The center nickel(II) ion and the lateral ones have octahedral and square‐planar coordination geometries, respectively. In the crystal, a three‐dimensional supramolecular network dominated by hydrogen bonds is observed. The reactivity toward DNA/protein bovine serum albumin (BSA) revealed that the complex could interact with herring sperm DNA (HS‐DNA) through the intercalation mode and quench the intrinsic fluorescence of BSA via a static mechanism. The in vitro anticancer activities suggested that the complex is active against the selected tumor cell lines.     

Antiproliferative Evaluation of Some 2‐[2‐(2‐Phenylethenyl)‐cyclopent‐3‐en‐1‐yl]‐1,3‐benzothiazoles: DFT and Molecular Docking Study

The 2‐[2‐(2‐phenylethenyl)cyclopent‐3‐en‐1‐yl]‐1,3‐benzothiazoles were synthesized from the reactions of 7‐benzylidenebicyclo[3.2.0]hept‐2‐en‐6‐ones with 2‐aminobenzenethiol. The antiproliferative activities of 2‐[2‐(2‐phenylethenyl)cyclopent‐3‐en‐1‐yl]‐1,3‐benzothiazoles were determined against C6 (rat brain tumor) and HeLa (human cervical carcinoma cells) cell lines using BrdU cell proliferation ELISA assay. Cisplatin and 5‐fluorouracil (5‐FU) were used as standards. The most active compound was 2‐{(1S,2S)‐2‐[(E)‐2‐(4‐methylphenyl)ethenyl]cyclopent‐3‐en‐1‐yl}‐1,3‐benzothiazole against C6 cell lines with IC₅₀=5.89 μm value (cisplatin, IC₅₀=14.46 μm and 5‐FU, IC₅₀=76.74 μm ). Furthermore, the most active compound was 2‐{(1S,2S)‐2‐[(E)‐2‐(2‐methoxyphenyl)ethenyl]cyclopent‐3‐en‐1‐yl}‐1,3‐benzothiazole against HeLa cell lines with IC₅₀=3.98 μm (cisplatin, IC₅₀=37.95 μm and 5‐FU, IC₅₀=46.32 μm ). Additionally, computational studies of related molecules were performed by using B3LYP/6‐31G+(d,p) level in the gas phase. Experimental IR and NMR data were compared with the calculated results and were found to be compatible with each other. Molecular electrostatic potential (MEP) maps of the most active 2‐{(1S,2S)‐2‐[(E)‐2‐(2‐methoxyphenyl)ethenyl]cyclopent‐3‐en‐1‐yl}‐1,3‐benzothiazole against HeLa and the most active 2‐{(1S,2S)‐2‐[(E)‐2‐(4‐methylphenyl)ethenyl]cyclopent‐3‐en‐1‐yl}‐1,3‐benzothiazole against C6 were investigated, aiming to determine the region that the molecule is biologically active. Biological activities of mentioned molecules were investigated with molecular docking analyses. The appropriate target protein (PDB codes: 1 M17 for the HeLa cells and 1JQH for the C6 cells) was used for 2‐{(1S,2S)‐2‐[(E)‐2‐(2‐methoxyphenyl)ethenyl]cyclopent‐3‐en‐1‐yl}‐1,3‐benzothiazole and 2‐{(1S,2S)‐2‐[(E)‐2‐(4‐methylphenyl)ethenyl]cyclopent‐3‐en‐1‐yl}‐1,3‐benzothiazole molecules exhibiting the highest biological activity against HeLa and C6 cells in the docking studies. As a result, it was determined that these molecules are the best candidates for the anticancer drug.