Synthesis,Characterization, and Biological Study of 3-Trifluoromethylpyrazole Tethered Chalcone-Pyrrole and Pyrazoline-Pyrrole Derivatives

The present study illustrates the design and synthesis of new series of 3-trifluoromethylpyrazole tethered chalcone-pyrrole and pyrazoline-pyrrole derivatives. All compounds were further screened for in vitro cytostatic activities on full NCI 60 cancer cell lines at National Cancer Institute, USA. Compounds (2E)-3-(1H-pyrrol-2-yl)-1-{4-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}prop-2-en-1-one ( 5a ) and (2E)-1-{3-methyl-4-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}-3-(1H-pyrrol-2-yl)prop-2-en-1-one ( 5c ) displayed significant antiproliferative activity (Growth Percentage: −77.10 and −92.13, respectively at 10 μM concentration) against the UO-31 cell lines from renal cancer and were further selected for assay at 10-fold dilutions of five different concentrations (10⁻⁴ to 10⁻⁸ M). Both compounds 5a and 5c exhibited promising antiproliferative activity (GI₅₀: 1.36 to 0.27 μM) against leukemia cancer cell lines HL-60 and RPMI-8226, colon cancer cell lines KM-12; breast cancer cell lines BT-549. Moreover, both compounds 5a and 5c were found to be non-cytotoxic (LC₅₀>100) against HL-60, RPMI-8226, and KM-12 cell lines. Remarkably, GI₅₀ values of compounds 5a and 5c were identified as more promising than sunitinib against most cancer cell lines. In silico study of compounds 5a and 5c exemplified the desired ADME properties for drug-likeness as well as tighter interactions with VEGFR-2. Hence, compounds 5a and 5c would be good cytotoxic agents after further clinical study.     

Novel Pyrazoloquinolin-2-ones: Design,synthesis, docking studies,and biological evaluation as antiproliferative EGFR-TK inhibitors

Two new series of diethyl 2-[2-(substituted-2-oxo-1,2-dihydroquinolin-4-yl)hydrazono]-succinates 6a-g and 1-(2-oxo-1,2-dihydroquinolin-4-yl)-1H-pyrazoles 7a-f have been designed and synthesized. The structures of the synthesized compounds were proved by IR, mass, NMR (2D) spectra and elemental analyses. The target compounds were evaluated for their in vitro cytotoxic activity against 60 cancer cell lines according to NCI protocol. Consequently, seven compounds were further examined against the most sensitive cell lines, leukemia CCRF-CEM, and MOLT-4. 5-Amino-1-(6-bromo-2-oxo-1,2-dihydroquinolin-4-yl)-1H-pyrazole-3,4-dicarbonitrile (7f) was the most active product, with IC₅₀ = 1.35 uM and 2.42 uM against MOLT-4 and CCRF-CEM, respectively. Also, it showed a remarkable inhibitory activity compared to erlotinib on the EGFR TK with IC₅₀ = 247.14 nM and 208.42 nM, respectively. Cell cycle analysis of MOLT-4 cells treated with 7f showed cell cycle arrest at G2/M phase (supported by Caspases, BAX and Bcl-2 studies) with a significant pro-apoptotic activity as indicated by annexin V-FITC staining. Moreover, the docking study indicated that both the pyrazole moiety and the quinolin-2-one ring showed good fitting into EGFR (PDB code: 1M17). In order to interpret SAR of the designed compounds, and provide a basis for further optimization, molecular docking of the synthesized compounds to known EGFR inhibitors was performed. The study illustrated the effect of several factors on the compounds’ activity.     

Anticancer evaluation and molecular modeling of multi-targeted kinase inhibitors based pyrido[2,3-d]pyrimidine scaffold

An efficient synthesis of substituted pyrido[2,3-d]pyrimidines was carried out and evaluated for in vitro anticancer activity against five cancer cell lines, namely hepatic cancer (HepG-2), prostate cancer (PC-3), colon cancer (HCT-116), breast cancer (MCF-7), and lung cancer (A-549) cell lines. Regarding HepG-2, PC-3, HCT-116 cancer cell lines, 7-(4-chlorophenyl)-2-(3-methyl-5-oxo-2,3-dihydro-1H-pyrazol-1-yl)-5-(p-tolyl)- pyrido[2,3-d]pyrimidin-4(3H)-one (5a) exhibited strong, more potent anticancer (IC₅₀: 0.3, 6.6 and 7?µM) relative to the standard doxorubicin (IC₅₀: 0.6, 6.8 and 12.8?µM), respectively. Kinase inhibitory assessment of 5a showed promising inhibitory activity against three kinases namely PDGFR β, EGFR, and CDK4/cyclin D1 at two concentrations 50 and 100?µM in single measurements. Further, a molecular docking study for compound 5a was performed to verify the binding mode towards the EGFR and CDK4/cyclin D1 kinases.     

Design,Synthesis, Anticancer Evaluation and Molecular Modeling Studies of New Thiazolidinone-Benzoate Scaffold as EGFR Inhibitors,Cell Cycle Interruption and Apoptosis Inducers in HepG2

Synthesis of new anticancer candidates with protein kinases inhibitory potency is a major goal of pharmaceutical science and synthetic research. This current work represents the synthesis of a series of substituted benzoate-thiazolidinones. Most prepared thiazolidinones were evaluated in vitro for their potential anticancer activity against three cell lines by MTT assay, and they found to be more effective against cancer cell lines with no harm toward normal cells. Thiazolidinones 5 c and 5 h were further evaluated to be kinase inhibitors against EGFR showing effective inhibitory impact (with IC₅₀ value; 0.2±0.009 and 0.098±0.004 μM, for 5 c and 5 h , respectively). Furthermore, 5 c and 5 h have effects on cell cycle and apoptosis induction capability in HepG2 cell lines by DNA-flow cytometry analysis and annexin V-FITC apoptosis assay, respectively. The results showed that they have effect of disrupting the cell cycle and causing cell mortality by apoptosis in the treated cells. Moreover, molecular docking studies showed better binding patterns for 5 c and 5 h with the active site of the epidermal growth factor receptor (EGFR) protein kinase (PDB code 1M17). Finally, toxicity risk and physicochemical characterization by Osiris method was performed on most of the compounds, revealing excellent properties as possible drugs.     

A novel piperazine linked β-amino alcohols bearing a benzosuberone scaffolds as anti-proliferative agents

A new series of 1-((9-chloro-2,3-dimethyl-6,7-dihydro-5H-benzo[7]annulen-8-yl)methoxy)-3-(4-phenylpiperzin-1-yl) propan-2-ols (6a-k) have been designed, synthesized and their structures were established by spectroscopic data (FT-IR, ¹H NMR, ¹³C NMR, HRMS) and further confirmed by X-ray analysis. The newly synthesized compounds 6a-k were evaluated for their in vitro anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MDA-MB-231 (breast), A549 (lung) and MIAPACA (pancreatic). Among the compounds tested, the compound 6e displayed most potent activity against four cancer cell lines with GI₅₀ values ranging from 0.010 to 0.097 μM. The structure and anti-proliferative activity relationship was further supported by in silico molecular docking study of the active compounds against Colchicine binding site of β-tubulin.     

Synthesis and SAR studies of bis-chromenone derivatives for anti-proliferative activity against human cancer cells

A novel family of 3-((4-oxo-4H-chromen-3-yl)methyl)-4H-chromen-4-one (bis-chromone) derivatives were designed, synthesized and studied for their anti-cancer activity using the XTT assay for the growth inhibition against various human cancer cells. Among them, 3-((5-(cyclohexylmethoxy)-4-oxo-4H-chromen-3-yl)methyl)-7-methoxy-4H-chromen-4-one and 3-((5-(cyclohexylmethoxy)-4-oxo-4H-chromen-3-yl)methyl)-7-hydroxy-4H-chromen-4-one showed micromolar level of in vitro anti-proliferative activity against human cancer cell lines. The SAR studies indicated bis-chromone as a basic scaffold to design anticancer agents. The 5-cyclohexylmethoxy on the first chromenone ring and electron donating group such as CH₃, OCH₃ or hydrogen bonding group (OH) on the other chromenone ring of bis-chromone increased the activity. However, saturation of one of chromenone to chromanone in bis-chromones decreased the activity.     

Synthesis,Cytotoxicity and Antimicrobial Evaluation of New Coumarin‐Tagged β‐Lactam Triazole Hybrid

A series of coumarin‐tagged β‐lactam triazole hybrids ( 10a – 10o ) were synthesized and tested for their cytotoxic activity against MDA‐MB‐231 (triple negative breast cancer), MCF‐7 (estrogen receptor positive breast cancer (ER+)) and A549 (human lung carcinoma) cancer cell lines including one normal cell line, HEK‐293 (human embryonic kidney). Two compounds 10b and 10d exhibited substantial cytotoxic effect against MCF‐7 cancer cell lines with IC₅₀ values of 53.55 and 58.62 μm , respectively. More importantly, compounds 10b and 10d were non‐cytotoxic against HEK‐293 cell lines. Structure–activity relationship (SAR) studies suggested that the nitro and chloro group at the C‐3 position of phenyl ring are favorable for anticancer activity, particularly against MCF‐7 cell lines. Furthermore, antimicrobial evaluation of these compounds revealed modest inhibition of examined pathogenic strains with compounds 10c and 10i being the most promising antimicrobial agents against Pseudomonas aeruginosa and Candida albicans, respectively.     

Synthesis,single crystal and antitumor activities of benzimidazole–quinazoline hybrids

A series of novel regioisomeric hybrids of quinazoline/benzimidazole viz. (3-allyl-2-methyl-3H-benzimidazol-5-yl)-(2-substituted-quinazolin-4-yl)-amine and (1-allyl-2-methyl-1H-benzimidazol-5-yl)-(2-substituted-quinazolin-4-yl)-amine of biological interest were synthesized. All the synthesized compounds were well characterized by ¹H and ¹³C NMR as well as mass spectroscopy. The newly synthesized compounds were screened for in vitro antitumor activities against 60 tumor cell lines panel assay. A significant inhibition for cancer cells were observed with compound 9 and also more active against known drug 5-fluorouracil (5-FU) in some tumor cell lines. Compound 9 displayed appreciable anticancer activity against leukemia, colon, melanoma, renal and breast cancer cell lines.     

Design,Synthesis and Cytotoxicity of New Coumarin-1,2,3-triazole Derivatives: Evaluation of Anticancer Activity and Molecular Docking Studies

A library of new coumarin-1,2,3-triazole hybrids 7a – l were synthesized from 4-(diethylamino)-2-hydroxybenzaldehyde precursor through a series of reactions including Vilsmeier-Haack reaction and condensation reaction to achieve key intermediate oxime and further performed click reaction by using different aromatic azides. We screened all molecules in silico against crystal structure of Serine/threonine-protein kinase 24 (MST3), based on these results all molecules were screened for their cytotoxicity against human breast cancer MCF-7 and lung cancer A-549 cell lines. Compound 7 b (p-bromo) showed best activity against both cell lines MCF-7 and A-549 with IC₅₀ value of 29.32 and 21.03 μM, respectively, in comparison to Doxorubicin corresponding IC₅₀ value of 28.76 and 20.82 μM. Another compound 7 f (o-methoxy) also indicated good activity against both cell lines with IC₅₀ value of 29.26 and 22.41 μM. The toxicity of all compounds tested against normal HEK-293 cell lines have not shown any adverse effects.     

Synthesis,anticancer and antioxidant activities of some novel N-(benzo[d]oxazol-2-yl)-2-(7- or 5-substituted-2-oxoindolin-3-ylidene) hydrazinecarboxamide derivatives

A series of N-(benzo[d]oxazol-2-yl)-2-(7- or 5-substituted-2-oxoindolin-3-ylidene) hydrazinecarboxamide derivatives were synthesized by treating N-(benzoxazol-2-yl)hydrazinecarboxamide with different isatin derivatives. The newly synthesized compounds were characterized on the basis of spectral analyses. All the synthesized derivatives (Va-l) were screened for anticancer and antioxidant activities. The results showed the anticancer activity of test compounds against HeLa, IMR-32 and MCF-7 cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. All the synthetic compounds produced a dose-dependant inhibition of growth of the cells. The IC₅₀ values of some compounds were comparable with standard anticancer agent, cisplatin. All the title compounds effectively scavenged the free radical, α,α-diphenyl-β-picryl hydrazyl. The test compounds having substitution with different halides (electron withdrawing groups) at C5 position showed more potent anticancer and antioxidant activities than those at C7 position. These results indicate that C5-substituted derivatives may be useful for developing antioxidant agents that play a protective role in many pathological conditions such as cancer, diabetes and so on.     

Analysis of Quinolinequinone Analogs with Promising Cytotoxic Activity against Breast Cancer

It is quite challenging to find out bioactive molecules in the vast chemical universe. Quinone moiety is a unique structure with a variety of biological properties, particularly in the treatment of cancer. In an effort to develop potent and secure antiproliferative lead compounds, five quinolinequinones ( AQQ1-5 ) described previously have been selected and submitted to the National Cancer Institute (NCI) of Bethesda to envisage their antiproliferative profile based on the NCI Developmental Therapeutics Program. According to the preliminary in vitro single-dose anticancer screening, four of five quinolinequinones ( AQQ2-5 ) were selected for five-dose screening and they displayed promising antiproliferative effects against several cancer types. All AQQs showed a excellent anticancer profile with low micromolar GI₅₀ and TGI values against all leukemia cell lines, some non-small cell lung and ovarian cancer, most colon, melanoma, and renal cancer, and in addition to some breast cancer cell lines. AQQ2-5 reduced the proliferation of all leukemia cell lines at a single dose and five additional doses, as well as some non-small cell lung and ovarian cancer, the majority of colon cancer, melanoma and renal cancer, and some breast cancer cell lines. This motivated us to use in vitro, in silico, and in vivo technologies to further investigate their mode of action. We investigated the in vitro cytotoxic activities of the most promising compounds, AQQ2 and AQQ3 , in HCT-116 colon cancer, MCF7 and T-47D breast cancer, and DU-145 prostate cancer cell lines, and HaCaT human keratinocytes. Concomitantly, IC₅₀ values of AQQ2 and AAQ3 against MCF7 and T-47D cell lines of breast cancer, DU-145 cell lines of prostate cancer, HCT-116 cell lines of colon cancer, and HaCaT human keratinocytes were determined. AQQ2 exhibited anticancer activity through the induction of apoptosis and caused alterations in the cell cycle. In silico pharmacokinetic studies of all analogs have been carried out against ATR, CHK1, WEE1, CDK1, and CDK2. In addition to this, in vitro ADME and in vivo pharmacokinetic profiling for the most effective AAQ ( AAQ2 ) have been studied.     

Synthesis of 2-(thienyl-2-yl or -3-yl)-4-furyl-6-aryl pyridine derivatives and evaluation of their topoisomerase I and II inhibitory activity,cytotoxicity, and structure–activity relationship

A series of 2-(thienyl-2-yl or -3-yl)-4-furyl-6-aryl pyridine derivatives were designed, synthesized, and evaluated for their topoisomerase I and II inhibition and cytotoxic activity against several human cancer cell lines. Compounds 10–19 showed moderate topoisomerase I and II inhibitory activity and 20–29 showed significant topoisomerase II inhibitory activity. Structure–activity relationship study revealed that 4-(5-chlorofuran-2-yl)-2-(thiophen-3-yl) moiety has an important role in displaying topoisomerase II inhibition.     

Synthesis,Antiproliferative Evaluation,and Molecular Docking Study of Novel Longifolene-Derived Tetraline Fused Thiazole-Amide Derivatives

Twenty novel longifolene-derived tetraline fused thiazole-amide compounds were synthesized from longifolene, a renewable natural resource. Their structures were characterized by FT-IR, NMR, ESI-MS, and elemental analysis. The in vitro antiproliferative activity of these compounds against SK-OV-3 ovarian cancer cell lines, MCF-7 human breast cancer cell lines, HepG2 human liver cancer cell lines, A549 human lung adenocarcinoma cell lines, and T-24 human bladder cancer cell lines was tested by MTT assay. Compounds 6a – 6c displayed significant and broad-spectrum antiproliferative activity against almost the tested cancer cell lines with IC₅₀ in the range of 7.84 to 55.88 μM, of which compound 6c exhibited excellent antiproliferative activities with 7.84 μM IC₅₀ against SKOV-3, 13.68 μM IC₅₀ against HepG2, 15.69 μM IC₅₀ against A549, 19.13 μM IC₅₀ against MCF-7, and 22.05 μM IC₅₀ against T-24, showing better and broad-spectrum antiproliferative effect than that of the positive control 5-FU. Furthermore, the action model was analyzed by the molecular docking study. Some intriguing structure-activity relationships were found and discussed herein by DFT theoretical calculation.     

New benzothieno[2,3-c]pyridines as non-steroidal CYP17 inhibitors: design,synthesis, anticancer screening,apoptosis induction,and in silico ADME profile studies

A series of [1]benzothieno[2,3-c]pyridines was synthesised. Most compounds were chosen by NCI-USA to evaluate their anticancer activity. Compounds 5a–c showed prominent growth inhibition against most cell lines. 5c was selected at five dose concentration levels. It exhibited potent broad-spectrum anticancer activity with a GI₅₀ of 4 nM–37 µM. Cytotoxicity of 5a–c was further evaluated against prostate, renal, and breast cancer cell lines. 5c showed double and quadruple the activity of staurosporine and abiraterone, respectively, against the PC-3 cell line with IC₅₀ 2.08 µM. The possible mechanism of anti-prostate cancer was explored via measuring the CYP17 enzyme activity in mice prostate cancer models compared to abiraterone. The results revealed that 5c suppressed the CYP17 enzyme to 15.80 nM. Moreover, it was found to be equipotent to abiraterone in testosterone production. Cell cycle analysis and apoptosis were performed. Additionally, the ADME profile of compound 5c demonstrated both good oral bioavailability and metabolic stability.     

Synthesis,Molecular Docking and Preliminary Antileukemic Activity of 4-Methoxybenzyl Derivatives Bearing Imidazo[2,1-b][1,3,4]thiadiazole

In this study, we synthesized 22 compounds in a series with various substitution on imidazo[2,1-b][1,3,4]thiadiazole. The potential cytotoxic activity of these compounds investigated in leukemia cell lines by Differential Nuclear Staining (DNS). Our results identified two compounds, 2-(4-methoxybenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl thiocyanate and 6-(4-chlorophenyl)-2-(4-methoxybenzyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde, exhibited the most cytotoxic effect against murine leukemia cells (L1210), human T-lymphocyte cells (CEM) and human cervix carcinoma cells (HeLa) with IC₅₀ values ranging between 0.79 and 1.6 μM. The results indicate that 2-(4-methoxybenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl thiocyanate is inducing phosphatidylserine externalization and caspase-3 activation which are both a hallmark of apoptosis. Docking studies showed that 2-(4-methoxybenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl thiocyanate binds within the active sites of transforming growth factor beta (TGF-β) type I receptor kinase domain by strong hydrogen binding and hydrophobic interactions.     

Design and synthesis of 2-(3-alkylaminophenyl)-6-(pyrrolidin-1-yl)quinolin-4-ones as potent antitumor agents

2-(3-Alkylaminophenyl)-6-(pyrrolidin-1-yl)quinolin-4-ones 1–3 were synthesized and screened for anti-proliferative activity against three human cancer cell lines, as well as the normal cell line Detroit 551. All of the synthesized target compounds 1–3 demonstrated potent cytotoxic activity against the cancer cell lines, but weak inhibitory activity toward the normal cell line. 2-(3-Methyl aminophenyl)-6-(pyrrolidin-1-yl)quinolin-4-one (1), one of the potent compounds in vitro, was also tested in an in vivo Hep3B xenograft nude mice model, and its significant anticancer activity was reconfirmed. Therefore, compound 1 merits further investigation as an antitumor clinical trial candidate and potential anticancer agent.     

Cytotoxicity and anticancer studies of Bacillus cereus and Bacillus pumilus metabolites targeting human cancer cells

The metabolites of bacteria Bacillus cereus and Bacillus pumilus isolated from soil samples in Shimoga region, Karnataka (India) were tested for cytotoxicity and anticancer properties. The various solvent extract fractions obtained from the metabolites of the two bacteria were tested for their cytotoxicity against normal human liver cell lines and 2 cancer cell lines by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole) assay. The two fractions obtained from B. cereus showed high cytotoxicity. These two fractions were further screened for anticancer activity by nuclear staining studies and DNA fragmentation analysis. Both the fractions demonstrated significant activity by membrane blebbing during nuclear staining and caused the damage the DNA patterns during DNA fragmentation analysis. On the other hand, the metabolites of B. pumilus revealed toxic effect against cancer cells as well as normal ones.     

Synthesis,in vitro antitumour activity,and molecular docking study of novel 2-substituted mercapto-3-(3,4,5-trimethoxybenzyl)-4(3H)-quinazolinone analogues

A novel series of 2-substituted mercapto-3-(3,4,5-trimethoxybenzyl)-4(3H)-quinazolinones 1–20 was synthesised and evaluated for in vitro antitumour activity. N-(4-Chlorophenyl)-2-[(3-(3,4,5-trimethoxybenzyl)-4(3H)-quinazolinon-2-yl)thio)acetamide (7) and N-(3,4,5 trimethoxybenzyl)-2-[(3-(3,4,5-trimethoxybenzyl)-4(3H)-quinazolinon-2-yl)thio]propanamide (19) exhibited excellent antitumour properties, with mean growth inhibitory concentration (GI₅₀) of 17.90 and 6.33 µΜ, respectively, compared with those of 5-fluorouracil 5-FU, gefitinib, and erlotinib (mean GI₅₀: 18.60, 3.24, and 7.29 µΜ, respectively). Comparison of the GI₅₀ (µM) values of compounds 7 and 19 versus those of 5-FU, gefitinib, and erlotinib against an in vitro subpanel of tumour cells lines showed that compounds 7 and 19 have activities almost equal to or higher than that of those standard drugs, especially against lung, CNS, and breast cancer cells. However, compounds 5, 10, 14, 15, 16, 17, and 20 exhibited effective antitumour activity against the different cell lines tested, with growth inhibition percentage (MGI%) of 19, 24, 19, 17, 16, 15, and 16, respectively. A modelling study was performed for compounds 7 and 19 by docking them into the EGFR kinase enzyme to study their mode of binding with the putative binding site.     

Synthesis of pro-apoptotic indapamide derivatives as anticancer agents

Abstract

4-Chloro-3-({[(substitutedamino)carbonothioyl]amino}sulfonyl)-N-(2-methyl-2,3-dihydro-1H-indole-1-yl)benzamide (1–20) and 4-chloro-3-({[3-(substituted)-4-oxo-1,3-thiazolidine-2-ylidene]amino}sulfonyl)-N-(2-methyl-2,3-dihydro-1H-indole-1-yl)benzamide derivatives (21–31) were synthesized from 4-chloro-N-(2-methyl-2,3-dihydroindol-1-yl)-3-sulfamoylbenzamide (indapamide). 4-Chloro-3-({[(4-chlorophenyl) amino) carbonothioyl]amino}sulfonyl)-N-(2-methyl-2,3-dihydro-1H-indole-1-yl)benzamide 12 demonstrated the highest proapoptotic activity among all synthesized compounds on melanoma cell lines MDA–MB-435 with 3.7% growth inhibition at the concentration of 10?µM. Compound 12 (SGK 266) was evaluated in vitro using the MTT colorimetric method against melanoma cancer cell line MDA–MB435 growth inhibition for different doses and exhibited anticancer activity with IC₅₀ values of 85–95?µM against melanoma cancer cell line MDA–MB435. In addition, this compound was investigated as inhibitors of four physiologically relevant human carbonic anhydrase isoforms, hCA I, II, IX and XII. The compund inhibited these enzymes with IC₅₀ values ranging between 0.72 and 1.60?µM.     

Synthesis of novel 5-(3-alkylquinolin-2-yl)-3-aryl isoxazole derivatives and their cytotoxic activity

The propargyl alcohol on reaction with aldoxime and NaOCl in DCM gave exclusively (3-arylisoxazol-5-yl) methanol 1. The compound 1 was oxidized to an aldehyde 2 followed by reaction with aniline resulted in Schiff’s base 3. The compounds 3 were further reacted with various aldehydes having α-hydrogen using molecular iodine as catalyst and which yielded 5-(3-alkylquinolin-2-yl)-3-aryl isoxazole derivatives 4. All the final compounds 4 were screened against four human cancer cell lines (A549, COLO 205, MDA-MB 231 and PC-3) and among these compounds 4n showed potent cytotoxicity against all the cell lines at IC₅₀ values of <12 μM.