A series of novel isolongifoleno7,8‐dthiazolo3,2‐apyrimidine derivatives (4a–4x) were synthesized from isolongifolanone according fragment‐based design strategy, and their anticancer activity against ...human aortic smooth muscle cells (HASMC), human breast cancer (MCF‐7) cells, human cervical cancer (HeLa) cells, and human liver cancer (HepG2) cells were investigated. Results of the anticancer activity illustrated that most of the compounds showed potent antitumor activity and compound 4i proved to be the most active derivative with IC50 values of 0.33 ± 0.24 (for MCF‐7 cells), 0.52 ± 0.13 (for HeLa cells), and 3.09 ± 0.11 μM (for HepG2 cells), respectively. Moreover, we assessed the effects of 4i on cell apoptosis, cell cycle distribution, mitochondrial membrane potential, and reactive oxygen species (ROS) generation. The results indicated that compound 4i altered mitochondrial membrane potential and produced ROS leading to cell apoptosis of MCF‐7 cells in a dose‐dependent manner, however, without affecting cell cycle progression. These findings suggested that 4i was an effective compound and provided a promising candidate for anticancer drugs.
24 new isolongifoleno7,8‐dthiazolo3,2‐apyrimidine derivatives (4a–4x) were synthesized. The compounds were evaluated for their antitumor activity. The compound 4i bearing 4‐fluorophenyl and 4‐methylphenyl was best active (IC50 = 0.33–3.09 μM). Compound 4i altered mitochondrial membrane potential and produced ROS leading to cell apoptosis of MCF‐7 cells in a dose‐dependent manner.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Ethyl 1-aminofuro(thieno)2,3-bpyridine-2-carboxylates 1 reacted with benzoyl isothiocyanate and gave the relevant thioureido derivatives 2, whose intramolecular cyclization under the action of ...potassium hydroxide furnished the relevant 9(10)-thioxopyrido3′,2′:4,5furo(thieno)3,2-dpyrimidin-7(8)-ones 3. Compounds 3 with methyl iodide could give the S-methyl 4 and S,N-dimethyl 5 derivatives. Interestingly 3 by alkylation with alkyl dichlorides (bifunctional reagents) the cyclization to a thiazoline or to a thiazine ring on the a side of the pyrimidine ring occurs, with formation of the new pentacyclic systems: furo(thieno)3,2-d1,3thiazolo3,2-apyrimidin-7(8)-ones 6 and furo(thieno)3′,2′:4,5pyrimido2,1-b1,3thiazin-7(8)-ones 7. Moreover compounds 3 by alkylation with p-chlorophenacyl bromide (again a bifunctional reagent) led to the formation of the corresponding S-alkylated compounds 9, whose cyclization furnished structural analogues of compounds 6: p-chlorophenyl-substituted thiazolo3,2-apyrimidin-7(8)-ones 10. The structure of the obtained compounds has been unambiguously confirmed by using a wide spectrum of physico-chemical methods and, in the instance of compounds 6 and 7, also by an alternative synthesis via a double-annelation reaction using a BMMA reagent. Biological tests have shown promising antimicrobial activity against Staphylococcus aureus for some of the synthesized compounds.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A novel series of thiazolo2,3-
bquinazoline (
14–
23,
26 and
27), and pyrido4,3-
dthiazolo3,2-
apyrimidine (
34–
43,
45 and
46) analogues were designed and synthesized. The obtained compounds were ...evaluated for their
in-vitro antitumor activity at the National Cancer Institute (NCI) 60 cell lines panel assay. Compounds
22,
38,
40 and
41 showed remarkable broad-spectrum antitumor activity. Compounds
22 and
38 are almost nine fold more active than 5-FU, with GI
50, TGI, and LC
50 values of 2.5, >100, >100; and 2.4, 9.1, 36.2 μM, respectively; while
40 and
41 are almost seven fold more active than 5-FU, with GI
50, TGI, and LC
50 values of 2.9, 12.4, 46.6 and 3.0, 16.3, 54.0 μM, respectively.
Compounds
22 and
38 are almost nine fold, while
40 and
41 are almost seven fold, more active than the known antitumor 5-FU.
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► Thiazolo2,3-
bquinazoline and pyrido4,3-
dthiazolo3,2-
apyrimidine analogues were synthesized. ►
In-vitro antitumor activity of the new compounds was evaluated. ► Compounds
22 and
38 are almost nine fold more active than 5-FU. ► Compounds
40 and
41 are almost seven fold more active than 5-FU.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
An efficient, simple and fast procedure has been developed for the synthesis of a novel types of pyrano2,3-
d
1,3thiazolo3,2-
a
pyrimidine derivatives through the one-pot three-component condensation ...reaction of 7-hydroxy-2,3-dihydro-5
H
-1,3thiazolo3,2-
a
pyrimidine-5-one, malononitrile and aromatic aldehydes in the presence DIPEA (N,N-diisopropylethylamine) as an available organo-base catalyst. This proposed procedure leads to the synthesis of desired products in short reaction times (5–10 min) and excellent isolated yields (90–94%).
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A series of 6-aryl-5-cyano-2-thiouracils was synthesized, the reaction of which with diethyl chloroethynylphosphonate leads to the selective formation of new 3-phosphonylated thiazolo3,2-
a
...pyrimidines. For the starting 6-aryl-5-cyano-2-thiouracils and their phosphonylated derivatives, antiviral activity against influenza A (H
1
N
1
) virus and cytotoxicity were studied.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Lung cancer (LC) ranks second most prevalent cancer in females after breast cancer and second in males after prostate cancer. Based on the GLOBOCAN 2020 report, India represented 5.9% of LC ...cases and 8.1% of deaths caused by the disease. Several clinical studies have shown that LC occurs because of biological and morphological abnormalities and the involvement of altered level of antioxidants, cytokines, and apoptotic markers. In the present study, we explored the antiproliferative activity of indeno1,2-dthiazolo3,2-apyrimidine analogues against LC using in-vitro, in-silico, and in-vivo models. In-vitro screening against A549 cells revealed compounds 9B (8-methoxy-5-(3,4,5-trimethoxyphenyl)-5,6-dihydroindeno1,2-dthiazolo3,2-apyrimidine) and 12B (5-(4-chlorophenyl)-5,6-dihydroindeno1,2-dthiazolo3,2-apyrimidine) as potential pyrimidine analogues against LC. Compounds 9B and 12B were docked with different molecular targets IL-6, Cyt-C, Caspase9, and Caspase3 using AutoDock Vina 4.1 to evaluate the binding affinity. Subsequently, in-vivo studies were conducted in albino Wistar rats through ethyl-carbamate (EC)- induced LC. 9B and 12B imparted significant effects on physiological (weight variation), and biochemical (anti-oxidant TBAR’s, SOD, ProC, and GSH), lipid (TC, TG, LDL, VLDL, and HDL), and cytokine (IL-2, IL-6, IL-10, and IL-1β) markers in EC-induced LC in albino Wistar rats. Morphological examination (SEM and H&E) and western blotting (IL-6, STAT3, Cyt-C, BAX, Bcl-2, Caspase3, and caspase9) showed that compounds 9B and 12B had antiproliferative effects. Accordingly, from the in-vitro, in-silico, and in-vivo experimental findings, we concluded that 9B and 12B have significant antiproliferative potential and are potential candidates for further evaluation to meet the requirements of investigation of new drug application.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The 1,3-dipolar cycloaddition reaction of ethyl (Z)-2-(2-methoxy-2-oxoethylidene)-7-methyl-3-oxo-5-aryl-2,3-dihydro-5
H
-thiazolo3,2-
a
pyrimidine-6-carboxylate and azomethine ylide which generated ...in situ by the reaction of isatin and 1,2,3,4-tetrahydroisoquinoline afforded novel 6′′-ethyl 2′-methyl-5′′-(aryl)-7′′-methyl-2,3′′-dioxo-6′,10b′-dihydro-2′
H
,3′′
H
,5′
H
,5′′
H
-dispiroindoline-3,3′-pyrrolo2,1-
a
isoquinoline-1′,2′′-thiazolo3,2-
a
pyrimidine-2′,6′′-dicarboxylate in moderate yields. The structures of all the products were characterized thoroughly by NMR, IR, HRMS together with X-ray crystallographic analysis.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Taking into account previously obtained biological results on some polyheterocyclic compounds (containing different heteroatoms) and in particular on several ...8-amino-5-isopropyl-2,2-dimethyl-10-(methylthio)-1,4-dihydro-2H-pyrano4'',3'':4',5'pyrido3',2':4,5thieno3,2-dpyrimidines Ia-v we have carried out the synthesis of twentyone 8-amino-5-isobutyl-2,2-dimethyl-10-(methylthio)-1,4-dihydro-2H-pyrano4'',3'':4',5'pyrido3',2':4,5thieno3,2-dpyrimidines 6. Therefore we have slightly modified the structure of the previously studied I introducing at C-5 an isobutyl group instead of the previously examined isopropyl ones in order to see if this variation (changing a little the lipophilicity) will affect the biological activity. Furthermore thieno3,2-dpyrimidine-8-thione 7 and their S-alkylated 8 were synthesized. Finally by alkylation of 5-isobutyl-2,2-dimethyl-10-thioxo-1,4,10,11-tetrahydro-2H-pyrano4'',3'':4',5'pyrido3',2':4,5thieno3,2-dpyrimidin-8(9H)-one 3 with alkyl dichlorides (bifunctional reagents) we realized the cyclization of a thiazole or thiazine ring on the b side of the pyrimidine ring with formation of the new condensed pentaheterocyclic systems: pyrano4'',3'':4',5'pyrido3',2':4,5thieno3,2-d1,3thiazolo3,2-apyrimidin-8-one 11 and pyrano4''',3''':4'',5''pyrido3'',2'':4',5'thieno3',2':4,5pyrimido2,1-b1,3thiazin-8-one 12. It was found that some of the synthesized compounds showed interesting antimicrobial activity (by agar diffusion method) against some gram-positive and gram-negative bacilli strains.
On the basis of some our previous results we have carried out the synthesis of several new polyheterocyclic compounds with the aim of studying their biological activity. Notwithstanding predictions from in silico tests furnished negative results, we have examined their antimicrobial activity (by agar diffusion methods) observing that several compounds showed very interesting activity. Then we can say that they represent new chemical entities.
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BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We present a novel, convenient, and efficient method for synthesizing polysubstituted 3-oxo-2,3-dihydro-5H-1,3thiazolo3,2-apyrimidines via a three-component reaction. The zwitterions generated from ...the reaction of isocyanides and dialkyl acetylenedicarboxylates react with 2-imino-1,3-thiazolidin-4-one to produce the title compounds in good yields.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
A facile method has been developed for the preparation of densely functionalized tricyclic fused pyrimidine derivatives by three-component 3+2+1 cyclization. Fairly good yields of the products (up to ...88%), the ready availability of the low-cost starting materials, the catalyst-free and mild conditions are the main advantages of this method.
Display omitted A facile three-component 3+2+1 cyclization protocol for the preparation of densely functionalized tricyclic fused pyrimidine derivatives has been designed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
