Synthesis of 2-substituted-6-(4<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazol-4-yl)benzo[<Emphasis Type="Italic">d</Emphasis>]oxazoles as potential anticonvulsant agents

A series of 2-substituted-6-(4H-1,2,4-triazol-4-yl)benzo[d]oxazoles were synthesized. The anticonvulsant effect and neurotoxicity of the compounds (intraperitoneally) were evaluated with the maximal electroshock (MES) test, subcutaneous pentylenetetrazole (sc-PTZ), and rotarod tests in mice. 2-Phenyl-6-(4H-1,2,4-triazol-4-yl)benzo[d]oxazole (3g) was the most active and also had the lowest toxicity. In the anti-MES potency test, it showed median effective dose (ED₅₀) of 29.5 mg/kg, a median toxicity dose (TD₅₀) of 285 mg/kg, and a protective index (PI) of 9.7, which is greater than the reference drug, carbamazepine, which has a PI of 6.4.     

Synthesis and anticonvulsant activity evaluation of 8-alkoxy-5-(4H-1,2,4-triazol-4-yl)quinoline derivatives

Two series of 8-alkoxy-5-(4H-1,2,4-triazol-4-yl)quinolines and 8-alkoxy-5-(2H-1,2,4-triazol-3-one-4-yl)quinolines were synthesized. The anticonvulsant activity of these compounds was evaluated with maximal electroshock seizure test and rotarod test. Among the synthesized compounds, 8-octoxy-5-(4H-1,2,4-triazol-4-yl)quinoline (4g) was the most active compound with ED₅₀ of 8.80 mg/kg, TD₅₀ of 176.03 mg/kg and protective index of 20.0. Its neurotoxicity was lower than all other synthesized compounds and also markedly lower than that of the reference drug carbamazepine. In addition, the potency of compound 4g against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid, and bicuculline suggested its broad spectrum activity, and the mechanisms of action including inhibition of voltage-gated ion channels and modulation of GABAergic activity might involve in its anticonvulsant activity.     

Synthesis and anticonvulsant evaluation of 3-substituted-4-(4-hexyloxyphenyl)-4H-1,2,4-triazoles

A series of 3-substituted-4-(4-hexyloxyphenyl)-4H-1,2,4-triazole derivatives (3a-s) were synthesized as open-chain analogues of 7-hexyloxyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolines (1c) using 4-hexyloxyaniline, acyl hydrazines, and dimethoxy-N,N-dimethylmethanamine as the starting material. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES test) and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox). MES test showed that all open-chain compounds exhibited strong anticonvulsant activity and lower neurotoxicity, and that some possessed obviously stronger activity than compound 1c. Compound 3d, 3-propyl-4-(4-hexyloxyphenyl)-4H-1,2,4-triazole was found to be the most potent with an ED₅₀ value of 5.7 mg/kg and protective index (PI = TD₅₀/ED₅₀) value of 11.5, which was much greater than that of the prototype drug phenytoin (PI = 6.9).     

Synthesis and anticonvulsant activity of 1-formamide-triazolo[4,3-<Emphasis Type="Italic">a</Emphasis>]quinoline derivatives

Using 6-hydroxy-3,4-dihydro-2(1H)-quinolone as the starting material, a series of 1-formamide-triazolo[4, 3-a]quinoline derivatives (6a-6n) was synthesized, the anticonvulsant effect and neurotoxicity of the compounds was calculated with maximal electroshock test and rotarod tests with intraperitoneally injected in KunMing mice. The results demonstrated that compound 7-(hexyloxy)-4,5-dihydro-[1,2,4] triazolo[4,3-a]quinoline-1-carboxamide (6d) was the most active one and also had the lowest toxicity. In the anti-maximal electroshock potency test, it showed median effective dose (ED₅₀) of 30.1 mg/kg, median toxicity dose (TD₅₀) of 286 mg/kg, and the protective index of 9.5 which is greater than the reference drug carbamazepine with the protective index value of 6.0.     

Synthesis and biological activity studies of new hybrid molecules containing tryptamine moiety

The synthesis of N′-(4-substitutedphenylsulfonyl)-2-{4-[2-(1H-indol-yl)ethyl]-3-(4-chlorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl}acetohydrazides (3a–c), 2-{4-[2-(1H-indol-3-yl)ethyl]-3-(4-chlorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl}-N′-aryl methylidene acetohydrazides (4a–f) and 4-[2-(1H-indol-3-yl)ethyl]-5-(4-substitutedbenzyl)-2-[(5-sulfanyl-1,3,4-oxadiazol-2-yl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-ones (5a, b) was performed starting from the corresponding acid hydrazides (2a, b) which was reported earlier. The treatment of 1,3,4-oxadiazole derivatives (5a, b) with hydrazine hydrate produced 4-amino-5-sulfanyl-4H-1,2,4-triazol-3-yl derivatives (6a, b). Then, compound 6b was converted to the corresponding Schiff base (7) by the treatment with anisaldehyde. The synthesis of 5-(4-chlorobenzyl)-4-[2-(1H-indol-3-yl)ethyl]-2-[(4-benzyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (8) and 5-(4-methylbenzyl)-4-[2-(1H-indol-3-yl)ethyl]-2-[(4-benzyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (10) was carried out by the reaction of acid hydrazides (2a, b) with aryl iso(thio)cyanates either via the formation of the intermediates (9a, b) (for 10) or direct cyclization (for 8). 1,3-Oxa(thia)zol-2(3H)-ylidene]acetohydrazide derivatives (11a, b) were obtained by the reaction of 9a, b with 4-chlorophenacyl bromide. All newly synthesized compounds were screened for their antimicrobial activities and some of which was found to be active against the test microorganisms.     

Synthesis of new 1,2,4-triazoles as anti-inflammatory and anti-nociceptive agents

A series of fifteen new substituted 1,2,4-triazoles (6a – 6o) have been synthesized in order to obtain new agents with potential anti-inflammatory and anti-nociceptive activity. The title compounds were synthesized using 4-methylbenzoic acid as a starting reactant. The synthesized compounds were characterized by spectroscopic methods (IR, ¹H NMR, ¹³ C NMR, FAB⁺ − MS) and elemental analysis (nitrogen analysis). The title compounds were evaluated for anti-inflammatory activity by the carrageenan induced paw edema method, and some compounds were evaluated for anti-nociceptive activity by the hot plate method and tail immersion method. Compounds N-[3-mercapto-5-(4-methylphenyl)-4H-1,2,4-triazol-4-yl]-2-piperidin-1-ylacetamide (6f), 2-(4-benzylpiperazin-1-yl)-N-[3-mercapto-5-(4-methylphenyl)-4H-1,2,4-triazol-4-yl]acetamide (6i) and N-[3-mercapto-5-(4-methylphenyl)-4H-1,2,4-triazol-4-yl]-2-morpholin-4-ylacetamide (6 k) showed significant anti-inflammatory activity compared to other synthesized compounds, and N-[3-mercapto-5-(4-methylphenyl)-4H-1,2,4-triazol-4-yl]-2-morpholin-4-ylacetamide (6 k) exhibited superior anti-nociceptive activity.     

Synthesis and anti-inflammatory activity evaluation of novel 3-alkyl-6-(4<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazol-4-yl)-3,4-dihydro-2<Emphasis Type="Italic">H</Emphasis>-benzo[<Emphasis Type="Italic">e</Emphasis>][1,3]oxazine derivatives

To discover new compounds with anti-inflammatory activity, a series of novel 3-alkyl-6-(4H-1,2,4-triazol-4-yl)-3,4-dihydro-2H-benzo[e][1,3]oxazine derivatives were synthesized and their structures were confirmed by spectroscopic techniques. In vivo anti-inflammatory activity of the synthesized compounds was determined using the xylene-induced mouse ear edema model. 3-Heptyl-6-(4H-1,2,4-triazol-4-yl)-3,4-dihydro-2H-benzo[e] [1,3]oxazine and 3-p-tolyl-6-(4H-1,2,4-triazol-4-yl)-3,4-dihydro-2H-benzo[e][1,3]oxazine demonstrated higher anti-inflammatory activity (74.04?% and 64.99?%, respectively) at 0.5?h after intraperitoneal administration than the reference drug ibuprofen (62.65?%). Further, the time of peak effect after oral administration was 4?h for both compounds. Our results identify new compounds with anti-inflammatory activity in vivo that may have improved safety/side effect profiles relative to the currently approved nonsteroidal anti-inflammatory drugs.     

Triazole antifungal agents

Patent Summary

Novel tri-substituted tetrahydrofurans are claimed to be antifungal agents. The compounds are stated to be particularly effective against Aspergillus and Candida.

Oral antifungal activity was assessed in mice. Against Aspergillus lung infection only one compound, for which data are presented, gave a survival rate of 100% (100 mg/kg).

Extensive synthetic details are provided and 42 compounds are exemplified. The most active is (-)-[(5R)-cis]-4-[4-[4-[4-[[5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)-tetrahydrofuran-3-yl]methoxy]phenyl]-1-piperazinyl]phenyl]-2,4-dihydro-2-[(1S)-(1-methylpropyl)]-3H-1,2,4-triazo-1-3-one.     

cAMP-dependent phosphodiesterase inhibition and SAR studies on novel 6,8-disubstituted 2-phenyl-3-(substituted benzothiazole-2-yl)-4[3H]-quinazolinone

Two series of 6,8-disubstituted-2-phenyl-3-(substituted benzothiazole-2-yl)-4[3H]-quinazolinone (1–13 and 14–26) were synthesized by reported method and evaluated for their phosphodiesterase inhibitory activity. All test compounds exhibited good activity. The structure–activity relationships based on the results obtained for these series were also studied. In both series, electron-withdrawing substitutions showed more activity. Among the tested compounds 6,8-dibromo-2-phenyl-3-(5-chloro benzothiazole-2-yl)-4[3H]-quinazolinone (20) and 6,8-dibromo-2-phenyl-3-(6-nitro benzothiazole-2-yl)-4[3H]-quinazolinone (24) were found to be even more potent than theophylline (IC₅₀ of 1438 ± 85 μM for 20 and 1520 ± 48 μM for 24). Presented at National Symposium on Challenges in Drug Discovery Research: Networking opportunities between Academia & Industries April 7th–8th, 2006 at Birla Institute of Technology & Science, Pilani and submitted to Nagpur University as an M-pharm thesis.     

Synthesis and antibacterial evaluation of 6-azapyrimidines with α-methylene-γ-(4-substituted phenyl)-γ-butyrolactone pharmacophores

Abstract  

A series of 6-substituted 2-[(4-methylene-5-oxo-2-(4-substituted phenyl) tetrahydrofuran-2-yl)methyl]-1,2,4-triazine-3,5(2H,4H)-diones (5, 6) and 2,4-bis[(4-methylene-5-oxo-2-(4-substituted phenyl) tetrahydrofuran-2-yl)methyl]-1,2,4-triazine-3,5(2H,4H)-diones (9, 10) were designed, synthesized, and evaluated for antibacterial activity against Gram-positive and Gram-negative microorganisms. The synthesis of these compounds involved the Reformatsky-type reaction between ethyl α-(bromomethyl)acrylate and the proper ketones. Among these compounds, 2-[(4-methylene-5-oxo-2-phenyl tetrahydrofuran-2-yl)methyl]-1,2,4-triazine-3,5(2H,4H)-dione (5a) is the most active compound and shown the selective inhibition activity against Proteus vulgaris.     

The Biotransformation of 8-Chloro-6-phenyl-4H-s-triazolo[4, 3-a][1,4] benzodiazepine (D-40TA), a New Central Depressant,in Man,Dog and Rat

1. Metabolic studies of 8-chloro-6-phenyl-4H-^s-triazolo [4,3-a] [1,4] benzodiazepine (D—40TA) in man, dog and rat led to identification of the following metabolites: six hydroxylation products; 8-chloro-2,4-dihydro-6-phenyl-1H-s-triazolo[4,3-a] [1,4]benzodiazepin-1-one (I), 8-chloro-6-(4-hydroxyphenyl)-4H-s -triazolo[4,3-a][1,4]benzodiazepine (II), 8-chloro-6- (3-hydroxyphenyl)-4H-s-triazolo[4,3-a] [1,4] benzodiazepine (III), 8-chloro-4-hydroxy-6-phenyl-4H-s- triazolo[4,3-a][1,4]benzodiazepine (IV), 8-chloro-2,4-dihydro-6- (4-hydroxy-phenyl)-1H-s-triazolo[4,3-a] [1,4] benzodiazepin-1-one (V) and 8-chloro-2,4-dihydro-6-(3-hydroxyphenyl)- 1H-s- triazolo[4,3-a][1,4]benzodiazepin-1-one (VI); five ring-opened metabolites; 5-chloro-2-(4H-1,2,4-triazol-4-yl) -benzophenone (VII), 5-chloro-2- (2,3-dihydro-3-oxo- 4H -1,2,4- triazol-4-yl)benzophenone (VIII), 5-chloro-2- (2,3-dihydro-3-oxo-4H - 1,2,4-triazol-4-yl)-2-hydroxybenzophenone (IX), 5-chloro-2- (2,3-dihydro-3-oxo-4H-1,2,4-triazol-4-yl)-4'-hydroxybenzophenone (X) and 5-chloro-2-(3,5-dioxo-2,3,4,5-tetrahydro-1H-1,2,4-triazol-4-yl) benzophenone(XI).

2. In man, metabolites I, IV, VII and VIII are present as the free form in the urine, and I, II, IV and VIII are present as conjugates. In the dog, all the metabolites are present. The rat transforms the compound mainly to metabolites I, II, IV and V. None of the ring-opened metabolites are observed in the rat.     

Synthesis and Evaluation of a New Series of 3,5-bis((5-bromo-6-methyl-2-t-aminopyrimidin-4-yl)thio)-4H-1,2,4-triazol-4-amines and their Cyclized Products ‘Pyrimidinylthio Pyrimidotriazolothiadiazines’ as 15- Lipo-Oxygenase Inhibitors

A series of new 3,5-bis((5-bromo-6-methyl-2-t-aminopyrimidin-4-yl)thio)-4H-1,2,4-triazol-4-amines and their cyclized products ‘pyrimidinylthio pyrimidotriazolothiadiazines’ were designed, synthesized, and evaluated as potential inhibitors of 15-lipo-oxygenase (15-LO). Their syntheses started by initial condensation of 2:1 equivalents of pyrimidine with triazole and subsequent nucleophilic displacement of the chlorine atoms with secondary amines and finally cyclocondensation in the presence of NaNH₂. The compounds 4d and 4f showed the best IC₅₀ of 15-LO inhibition (IC₅₀ = 9 and 12 μm , respectively). Compounds 4a – g were docked into 15-LO. We suggest that the hydrogen bonds in quaternary nitrogen of piperazine ring of compounds 4d and 4f appear to play major role in lipo-oxygenase inhibition by this set of synthesized analogs and hydrophobic nature of this protein's binding site should be considered in ongoing investigations.     

Patent Evaluation: Trisubstituted tetrahydrofuran antifungal agents

Summary

Novelty: Novel tri-substituted tetrahydrofurans, stated to have potential utility as antifungal agents, are disclosed.

Biology: A range of in vivo rodent studies demonstrating pharmacological efficacy are presented. These include evaluation of antifungal activity using an Aspergillus pulmonary infection model. Oral treatment (100mg/kg/day) was initiated 24 hours post-infection and maintained for 4 days. A preferred test compound was found to have greater antifungal activity than itraconazole, fluconazole and saperconazole. Results are presented in figures.

Chemistry:(-)-[(5R)-cis]-4-[4-[4-[4-[[5-(2-4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl) tetrahydofuran-3-yl]methoxy]phenyl-1-piperazinyl]phenyl]-2,4-dihydro-2[(S)-(1-methylpropyl)]-3H-1,2,4,-triazol-3-one is one of thirty compounds specifically exemplified. Full preparative details using standard techniques are presented.     

Design and synthesis of some novel 3-[5-(4-substituted) phenyl-1,3,4-oxadiazole-2yl]-2-phenylquinazoline-4(3H)-ones as possible anticonvulsant agent

A novel series 7(a–f) 3-[5-(4-substituted) phenyl-1,3,4-oxadiazole-2yl]-2 phenylquinazoline-4(3H)-ones have been synthesized and screened for its anticonvulsant and neurotoxic activity. After i.p. injection to mice at doses of 30, 100, and 300 mg/kg body weight 2,3-disubstituted-quinazolin-4(3H)-ones were examined in the maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. Spectroscopic data were consistent with the structure of newly synthesized compounds. The neurotoxicity was assessed using the rotorod method. In the prepared series, 7a was found to be active in the MES screen at 0.5 h, whereas 7f showed anticonvulsant activity at both 0.5 and 4 h.     

Design, synthesis, and potential CNS activity of some new bioactive 1-(4-substituted-phenyl)-3-(4-oxo-2-methyl-4H-quinazolin-3-yl)-urea

Twelve new 1-(4-substituted-phenyl)-3-(4-oxo-2-methyl-4H-quinazolin-3-yl)-urea were synthesized and screened for anticonvulsant, CNS depressant, and sedative-hypnotic activity. After i.p. injection to mice at doses of 30, 100, and 300 mg/kg body weight 2,3-Disubstituted-quinazolin-4(3H)-one were examined in the maximal electroshock-induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. Spectroscopic data and elemental analysis were consistent with the newly synthesized compounds. The neurotoxicity was assessed using the rotorod method. M3, M4, and M10 were found to be active in both MES screen and scPTZ screen at 0.5 h. All except M11 showed more than 44% decrease in locomotor activity after 1 h of compound administration via actophotometer screen. CNS-depressant activity screened with the help of the forced swim method resulted into some potent compounds. Except for M6 and M11 other tested compounds were found to exhibit potent CNS depressants activity as indicated by increased immobility time. It can be concluded that newly synthesized compounds possessed sedative-hypnotic and CNS depressant activities.     

Synthesis and antiviral activity of new 4-(phenylamino)/4-[(methylpyridin-2-yl)amino]-1-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acids derivatives

The synthesis of new 4-(phenylamino)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (3a-l) derivatives and the new 4-[(methylpyridin-2-yl)amino]-1-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (5a–c) derivatives was achieved with an efficient synthetic route. Ethyl 4-chloro-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate (1) on fusion with appropriate substituted anilines or aminopicolines gave the required new ethyl 4-(phenylamino)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylates (2a–l) (52–82%) or new ethyl 4-[(methylpyridin-2-yl)amino]-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylates (4a–c) (50–60%), respectively. Subsequent hydrolysis of the esters afforded the corresponding carboxylic acids (3a–l) (86–93%) and (5a–c) in high yield (80–93%). Inhibitory effects of 4-(phenylamino)/4-[(methylpyridin-2-yl)amino]-1-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acids. Derivatives on Herpes simplex virus type 1 (HSV-1), Mayaro virus (MAY) and vesicular stomatitis virus (VSV) were investigated. Compounds 2d, 3f, 3a, and 3c exhibited antiviral activity against HSV-1, MAY, and VSV virus with EC₅₀ values of 6.8, 2.2, 4.8, 0.52, 2.5, and 1.0. None of these compounds showed toxicity for Vero cells.     

Synthesis and Evaluation of Antidepressant-like Activity of Some 4-Substituted 1-(2-methoxyphenyl)Piperazine Derivatives

A series of new derivatives of N-(2-methoxyphenyl)piperazine have been synthesized for their affinity toward serotonergic receptors and for their potential antidepressant-like activity. They have been evaluated toward receptors 5-HT_1A, 5-HT₆, and 5-HT₇, as well as in vivo in the tail suspension, locomotor activity, and motor co-ordination tests. All the tested compounds proved very good affinities toward 5-HT_1A and 5-HT₇ receptors. The most promising compound was 1-[(2-chloro-6-methylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride, exhibiting affinity toward receptors K_i <1 nm (5-HT_1A) and K_i = 34 nm (5-HT₇). Antidepressant-like activity (tail suspension test) was observed at 2.5 mg/kg b.w. (mice, i.p.), and the effect was stronger than that observed for imipramine (5 mg/kg b.w.). Sedative activity was observed at ED₅₀ (locomotor test, mice, i.p.) = 17.5 mg/kg b.w. and neurotoxicity was observed at TD₅₀ (rotarod, mice, i.p.) = 53.2 mg/kg b.w.     

Synthesis and antimicrobial activity of new 1-[(tetrazol-5-yl)methyl] indole derivatives,their 1,2,4-triazole thioglycosides and acyclic analogs

New 1-[(tetrazol-5-yl)methyl]indole derivatives, their acyclic nucleoside analogs and the corresponding glycoside derivatives were synthesized. Furthermore, the [)(1,2,4-triazol-3-yl)methyl])-2H-tetrazole derivative as well as the corresponding thioglucoside were prepared. The synthesized compounds were tested for their antimicrobial activity against Aspergillus Niger, Penicillium sp, Candida albican, Bacillus subtilis, Streptococcus lacti, Escherichia coli, Pseudomonas sp., and streptomyces sp. Compounds 3, 5 and 19b exhibited potent antibacterial activity and compounds 4, 5 and 10 exhibited high activities against the tested fungi compared with fusidic acid.     

Synthesis and Anticonvulsant Activity of 5‐Phenyl‐[1,2,4]‐triazolo[4,3‐a]quinolines

A series of novel 5‐phenyl‐[1,2,4]‐triazolo[4,3‐a]quinoline derivatives was synthesized by the cyclization of 2‐chloro‐4‐phenyl‐1,2‐dihydronaphthalene with formohydrazide. The starting material 2‐chloro‐4‐phenyl‐1,2‐dihydronaphthalene was synthesized from ethyl‐3‐oxo‐3‐phenylpropanoate and substituted aniline. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox). The maximal electroshock test showed that 7‐hexyloxy‐5‐phenyl‐[1,2,4]‐triazolo[4,3‐a]quinoline 4f was found to be the most potent compound with an ED₅₀ value of 6.5 mg/kg and a protective index (PI = ED₅₀ / TD₅₀) value of 35.1, which was much higher than the PI of the reference drug phenytoin.     

Design,synthesis, docking study and cytotoxic activity evaluation of some novel letrozole analogs

Background

Breast cancer is the most common type of female cancer. One class of hormonal therapy for breast cancer drugs -non steroidal aromatase inhibitors- are triazole analogues. In this work, some derivatives of these drugs was designed and synthesized. All synthesized compounds were evaluated for their cytotoxic activities on breast cancer cell lines (MDA-MB-231, T47D and MCF-7).

Methods

Our synthetic route for designed compounds started from 4-bromotolunitrile which was reacted with 1H-1,2,4-triazole to afford 4-(4-cyanobenzyl)-1,2,4-triazole. The reaction of later compound with aromatic aldehydes led to formation of the designed compounds. Eleven novel derivatives 1a-k were tested for their cytotoxic activities on three human breast cancer cell lines.

Results

Among the synthesized compound, 4-[2-(3-chlorophenyl)-1-(1H-1,2,4-triazol-1-yl)ethenyl]benzonitrile (1c) showed the highest activity against MCF-7 and MDA-MB-231 cell lines and 4-[2-(4-methoxyphenyl)-1-(1H-1,2,4-triazol-1-yl)ethenyl]benzonitrile (1 h) exhibited highest activity against T47D cell line. According to cytotoxic activities results, compound 4-[2-(4-dimethylamino)-1-(1H-1,2,4-triazol-1-yl)ethenyl]benzonitrile (1 k) showed comparative activity against T47D and MDA-MB-231 cell lines with compound (1 h) and our reference drug Etoposide.

Conclusion

In the process of anti-cancer drug discovery, to find new potential anti-breast cancer agents, we designed and synthesized a novel series of letrozole analogs. Cytotoxicity evaluation revealed that compounds (1c) and (1 k) were the most potent compounds with comparative activity with Etoposide. The results revealed that π-π interactions are responsible for the enzyme inhibitions of compounds (1 c) and (1 k).Keyword: Breast cancer, Non-steroidal aromatase inhibitor, Cytotoxic activity