Design, in silico studies, synthesis, and in vitro anticancer assessment of new naphthylidene isoxazolidinedione derivatives

. In vitro biological evaluation revealed the most active compound 4d with an inhibitory concentration of 42.87 μM against K562 and 47.42 μM on A549 cells. The anticancer activity of this naphthylidene isoxazolidinedione derivative was evident by cell cycle and apoptosis assays, which showed arrest of the G2/M phase (65.6%) of the K562 cells and induction of apoptosis with 21.47% apoptotic cells as compared to 0.2% of untreated cells, respectively.
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Design, in silico studies, synthesis, and in vitro anticancer assessment of new naphthylidene isoxazolidinedione derivativesReceived: 21 April 2023 Revised: 27 September 2023 Accepted: 7 October 2023DOI: 10.1002/vjch.202300148RESEARCH ARTICLEDesign, in silico studies, synthesis, and in vitro anticancerassessment of new naphthylidene isoxazolidinedionederivativesNeha Upadhyay1 Kalpana Tilekar1 Aditi Oak1 Vadim S. Pokrovsky2,3Ramaa Subramanian Chelakara11 Department of Pharmaceutical Chemistry,Bharati Vidyapeeth’s College of Pharmacy, CBD AbstractBelapur, Navi Mumbai, India Cancer is the most destructive and fatal disease, representing an urgent med-2 Laboratory of Biochemical Fundamentals of ical challenge to the world. The discovery of a new anticancer candidate mayPharmacology and Cancer Models, N. N. Blokhin help reduce or eliminate this alarming disease to a greater extent. On similarCancer Research Center, Moscow, Russia lines, in silico research was carried out on novel naphthylidene isoxazolidinedione3 Department of Biochemistry, People’s derivatives that were logically conceived, synthesized, purified, and structurallyFriendship University, Moscow, Russia characterized. In vitro biological evaluation revealed the most active compoundCorrespondence 4d with an inhibitory concentration of 42.87 μM against K562 and 47.42 μMRamaa Subramanian Chelakara, Department of on A549 cells. The anticancer activity of this naphthylidene isoxazolidinedionePharmaceutical Chemistry, Bharati Vidyapeeth’s derivative was evident by cell cycle and apoptosis assays, which showed arrest ofCollege of Pharmacy, CBD Belapur, Navi Mumbai400614, India. the G2/M phase (65.6%) of the K562 cells and induction of apoptosis with 21.47%Email: sinharamaa@yahoo.in apoptotic cells as compared to 0.2% of untreated cells, respectively.Funding information KEYWORDSASEAN-India S&T Development Fund (AISTDF), antiproliferative, apoptosis, bio-isostere, cell cycle, isoxazolidinedioneGrant/Award Number:IMRC/AISTDF/CRD/2018/0000011 INTRODUCTION incorporated a common pharmacophoric feature, which is a heterocyclic ring, “2,4-thiazolidinedione (TZD)” as aCancer is a multigenic and multifactorial disease that is one central or peripheral moiety that significantly contributedof the most serious menaces to the human race. Though to antitumor activity by targeting single or multiplecurrently available therapies are effective for the treatment cancer hallmarks.5–15 However, we also published com-of early stages of cancer, patient survival remains limited pounds without the TZD nucleus showing good antipro-due to various factors such as toxicity, drug resistance, liferative activity (Figure 1).16–25 Interestingly, there areetc.1,2 Considering the cancer epidemiology and its notori- countless pieces of literature demonstrating compoundsously convoluted biology, it is an alarming condition as only with anticancer activity incorporating various heterocyclicscanty actives reach the clinical stage.3,4 Thus, continuous rings.17,19,25–30 On a similar path, we have recently reportedefforts are ongoing to explore various new therapeutics to new small molecules incorporating heterocyclic rings, imi-successfully combat the disease. Among these discoveries, dazolidinedione, and pyrrolidinedione showing excellentthe development of synthetic chemical entities has been antitumor activity.19,26 Therefore, with our previous expe-considered a source for the discovery of anticancer small rience and knowledge, by considering the structural mod-molecules. ification of our previously reported analogs, we developed We have previously reported numerous compounds compounds incorporating the TZD bio-isostere which is awith antiproliferative potential targeting various essen- heterocyclic ring isoxaz ...