Novel 2-benzylthio-5-(1,3,4-oxadiazol-2-yl)benzenesulfonamides with anticancer activity: Synthesis, QSAR study, and metabolic stability

Sławiński, Jarosław; Szafrański, Krzysztof; Pogorzelska, Aneta; Żołnowska, Beata; Kawiak, Anna; Macur, Katarzyna; Belka, Mariusz; Bączek, Tomasz

doi:10.1016/j.ejmech.2017.03.039

Cited by 48 publications

(17 citation statements)

References 30 publications

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“…This basic approach led to statistically insignificant equations, so it was decided to apply multivariate PLS and OPLS techniques using SIMCA software [ 36 , 37 ]. Such an approach enabled to achieve valuable information in one of our previous reports [ 38 ]. Before regression analysis compounds with outlying cytotoxicity values were excluded.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 2-alkylthio-N-(quinazolin-2-yl)benzenesulfonamide derivatives: anticancer activity, QSAR studies, and metabolic stability

et al. 2018

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A new series of 2-alkylthio-N-(quinazolin-2-yl)benzenesulfonamide derivatives have been synthesized and evaluated in vitro for their antiproliferative activity by MTT assay against cancer cell lines HCT-116, MCF-7, and HeLa as well as the NCI-60 human tumor cell lines screen. In NCI screen, three compounds inhibited approximately 50% growth of RPMI-8226 and A549/ATCC cell lines. The mean of IC50 calculated in MTT assays for three tested cell lines was about 45 μM for four compounds. The QSAR allowed finding statistically significant OPLS models for HeLa cell line. Metabolic stability in vitro studies indicated favorable and unfavorable structural elements. The good metabolic stability, with t1/2 higher than 40 min, was observed for three derivatives, which together with their antiproliferative activity and good ADMET profile, makes them good leading structures for further research.Graphical abstract

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Section: Resultsmentioning

confidence: 99%

Synthesis of 2-alkylthio-N-(quinazolin-2-yl)benzenesulfonamide derivatives: anticancer activity, QSAR studies, and metabolic stability

et al. 2018

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“…In general, when R 1 = Cl, selectivity index SI (which represents IC 50 for HaCaT cell line/IC 50 for cancerous cell line) for active derivatives (for which IC 50 for cancer line ≤ 25 µM) is in the range from 2 to 16, depending on the cell line. Meanwhile, if R 1 is SBn, it reaches 13 (14) and 22 (35); however, in this group there are also several cases (8,10,18) where activity against HaCaT is at the same level as against cancer lines.…”

Section: Structure-activity Relationshipmentioning

confidence: 93%

“…Recently, we described how the treatment of 2,4-dichloro-5-(carbazoyl)benzenesulfonamide 1 with phenylmethanethiol in the presence of tetrabutylammonium iodide (TBAI) as a phase transfer catalyst resulted in the selective substitution of chlorine atom in position 2 of the benzene ring, yielding 2-benzylthio-4-chloro-5-(carbazoyl)benzenesulfonamide 2 [18]. Then, reacting hydrazide 1 or 2 with triethyl orthochloroacetate led to a cyclization product, i.e., corresponding 2-(chloromethyl)-1,3,4-oxadiazole derivatives 4 or 3 (Scheme 1).…”

Section: Chemistrymentioning

confidence: 99%

“…Synthesis and spectral data for compounds 2, 3, 6, 8, 10, 12, 14 and 16 were reported in our previous work [18].…”

Section: Synthesismentioning

confidence: 99%

“…Our efforts for a long time have been focused on extensive research on the antineoplastic activity of 2-mercaptobenzenensulfonamide derivatives [14][15][16][17]. Recently, we synthesized a large group of 2-(benzylthio)-4-chloro-5-[(5-(substituted)-1,3,4-oxadiazol-2-yl)]benzenesulfonamides, and found that among them a series of (E)-2-(benzylthio)-4-chloro-5-(5-styryl-1,3,4-oxadiazol-2-yl)benzenesulfonamides display significant antitumor activity [18].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, Anticancer Evaluation and Structure-Activity Analysis of Novel (E)- 5-(2-Arylvinyl)-1,3,4-oxadiazol-2-yl)benzenesulfonamides

Szafrański

Sławiński

Tomorowicz

et al. 2020

IJMS

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To learn more about the structure–activity relationships of (E)-3-(5-styryl-1,3,4-oxadiazol-2-yl)benzenesulfonamide derivatives, which in our previous research displayed promising in vitro anticancer activity, we have synthesized a group of novel (E)-5-[(5-(2-arylvinyl)-1,3,4-oxadiazol-2-yl)]-4-chloro-2-R1-benzenesulfonamides 7–36 as well as (E)-4-[5-styryl1,3,4-oxadiazol-2-yl]benzenesulfonamides 47–50 and (E)-2-(2,4-dichlorophenyl)-5-(2-arylvinyl)-1,3,4-oxadiazols 51–55. All target derivatives were evaluated for their anticancer activity on HeLa, HCT-116, and MCF-7 human tumor cell lines. The obtained results were analyzed in order to explain the influence of a structure of the 2-aryl-vinyl substituent and benzenesulfonamide scaffold on the anti-tumor activity. Compound 31, bearing 5-nitrothiophene moiety, exhibited the most potent anticancer activity against the HCT-116, MCF-7, and HeLa cell lines, with IC50 values of 0.5, 4, and 4.5 µM, respectively. Analysis of structure-activity relationship showed significant differences in activity depending on the substituent in position 3 of the benzenesulfonamide ring and indicated as the optimal meta position of the sulfonamide moiety relative to the oxadizole ring. In the next stage, chemometric analysis was performed basing on a set of computed molecular descriptors. Hierarchical cluster analysis was used to examine the internal structure of the obtained data and the quantitative structure–activity relationship (QSAR) analysis with multiple linear regression (MLR) method allowed for finding statistically significant models for predicting activity towards all three cancer cell lines.

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Oxidative Cyclization of N‐Aryl Heteroaryl Methanamines with Arylalkenes

Sang

Huo

2023

Adv Synth Catal

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Novel 2-benzylthio-5-(1,3,4-oxadiazol-2-yl)benzenesulfonamides with anticancer activity: Synthesis, QSAR study, and metabolic stability

Cited by 48 publications

References 30 publications

Synthesis of 2-alkylthio-N-(quinazolin-2-yl)benzenesulfonamide derivatives: anticancer activity, QSAR studies, and metabolic stability

Synthesis of 2-alkylthio-N-(quinazolin-2-yl)benzenesulfonamide derivatives: anticancer activity, QSAR studies, and metabolic stability

Synthesis, Anticancer Evaluation and Structure-Activity Analysis of Novel (E)- 5-(2-Arylvinyl)-1,3,4-oxadiazol-2-yl)benzenesulfonamides

Oxidative Cyclization of N‐Aryl Heteroaryl Methanamines with Arylalkenes

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