Saleh I. Alqasoumi

Synthesis of some new pyrazolo[3,4-d]pyrimidine derivatives of expected anticancer and radioprotective activity

On the account of the reported anticancer activity of pyrazolo[3,4-d]pyrimidines, a new series of pyrazolo[3,4-d]pyrimidine derivatives were synthesized and tested for in-vitro anticancer activity against Ehrlich Ascites Carcinoma (EAC) cell line. Moreover, one of the target products was evaluated for in-vivo radioprotective activity. The reaction of o-aminoester 1 with benzylamine in presence of triethylorthoformate yielded the corresponding 5-benzylpyrazolopyrimidine derivative 2. The N-amino derivative 3 was used to synthesize new derivatives of pyrazolopyrimidines 4-7. The corresponding 1,3,4-oxadiazolopyrazolopyrimidine derivatives 12 and 14 were obtained via reaction of compound 9 with reagent 10 and/or triethylorthoformate. Thiophosgenation of compound 1 furnished the corresponding 5-isothiocyanate derivative 15, which was reacted with o-phenylenediamine, thiosemicarbazide and anthranilic acid to give benzimidazolopyrazolopyrimidine, 17, pyrazolotriazolopyrimidine, 19 and pyrazolopyrimidobenzoxazine, 20 respectively. The structures of the synthesized compounds were confirmed by microanalyses, IR, NMR, and mass spectral data. Compounds 2 and 9 showed intermediate anticancer activity compared to doxorubicin as positive control with IC50 values of 90 and 100 microg/ml, respectively. On the other hand, compound 5 showed significant radioprotective effect.

Novel quinolines and pyrimido[4,5-b]quinolines bearing biologically active sulfonamide moiety as a new class of antitumor agents

Some novel quinolines and pyrimido[4,5-b]quinolines have been synthesized. The structures of which were confirmed by elemental analyses and spectral data. All the target compounds were subjected to in-vitro antitumor activity against Ehrlich Ascites Carcinoma (EAC) cells. Compounds 24, 19 and 12 showed higher activity with IC(50) values (5.5, 6.9, 7 microg/ml) when compared with Doxorubicin as a reference drug (IC(50) value 38 microg/ml).

Synthesis and in vitro anticancer screening of some novel 4-[2-amino-3-cyano-4-substituted-5,6,7,8-tetrahydroquinolin-1-(4H)-yl]benzenesulfonamides.

It has been reported that aryl/heteroaryl sulfonamide compounds may act as anticancer agents through a variety of mechanisms and the most prominent of these mechanisms is through the inhibition of carbonic anhydrase isozymes. The present work reports the possible utility of 4-(cyclohexenylamino)benzenesulfonamide in the synthesis of some novel 4-(quinolin-1-yl)benzenesulfonamide derivatives 6a-u. The structures of these compounds were confirmed by elemental analyses, IR, (1)H NMR and mass spectral data. All the newly synthesized compounds were evaluated for their in vitro anticancer activity. Some compounds showed interesting in vitro anticancer activities when compared with doxorubicin as a reference drug. In addition, docking of the synthesized compounds into carbonic anhydrase isozyme II (CA II) active site was performed in order to give a suggestion about the proposed mechanism of action.

Synthesis and biological evaluation of 2-amino-7,7-dimethyl 4-substituted-5-oxo-1-(3,4,5-trimethoxy)-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile derivatives as potential cytotoxic agents

A large number of antimitotic drugs, derived from natural sources or chemically synthesized, have been identified and shown to interfere with the tubulin system. Inhibition of tubulin polymerization is among the important targets useful in the cancer therapy. The present work reports the synthesis of some novel quinoline derivatives bearing a trimethoxyphenyl moiety. The trimethoxybenzene moiety has been reported to be crucial to obtain relevant cytotoxic and antitubulin responses. All the newly synthesized compounds were evaluated for their in vitro anticancer activity. Several compounds showed interesting cytotoxic activities compared to the used reference drug.

Discovering some novel tetrahydroquinoline derivatives bearing the biologically active sulfonamide moiety as a new class of antitumor agents.

The present article describes the synthesis of some novel 4-(2-amino-3-cyano-4-(substituted-aryl)-5-oxo-5,6,7,8-tetrahydroquinolin-1(4H)-yl)benzenesulfonamide (23-41) starting with 4-(3-oxo-cyclohex-1-enylamino)benzenesulfonamide (3). All the newly synthesized compounds were evaluated for their in vitro antitumor activity. Compounds 32, 25, 41, 35, 33, and 37 with IC50 values (2.5, 3, 5, 10, 12, and 12.5 microg/mL) are more potent and efficacious than Doxorubicin (CAS-23214-92-8) as reference drug with (IC50 value=37.5 microg/mL). Also, compounds 28, 30, 31, and 34 (with IC50 values=25 microg/mL) are nearly as active as Doxorubicin.

Quinazoline-tyrphostin as a new class of antitumor agents, molecular properties prediction, synthesis and biological testing

A new series of substituted quinazolin-4-(3H)-one-tyrphostin derivatives was prepared and screened for their cytotoxic activity against three tumor cell lines, namely human breast cancer cell line (MCF-7), human cervical cancer cell line (HeLa) and human hepatocellular liver carcinoma cell line (HepG2) using the colorimetric MTT assay. Among the current series, 10 compounds exhibited remarkable in vitro antiproliferative activity against the three tested cell lines with the IC(50) values ranging from 0.009 to 0.015 mM. All the compounds showed suitable drug like characteristics according to Lipinskis rule.

Gastric antiulcer, antisecretory and cytoprotective properties of celery (Apium graveolens) in rats

In the present investigation, an ethanol extract of celery [Apium graveolens L. (Apiaceae/Umbelliferae)], at doses of 250 and 500 mg/kg body weight, was evaluated for antigastric ulcer activity using various experimental gastric ulcer models in rats. Ulcers were induced by indomethacin, cytodestructive agents (80% ethanol, 0.2 M NaOH and 25% NaCl) and cold restraint stress. Gastric secretory studies were undertaken by using pylorus ligation (Shay rat model). In addition to gastric wall mucus (GWM), non-protein sulfhydryl (NP-SH) and malondialdehyde (MDA) were also estimated in gastric tissues after 80% ethanol treatment. Pretreatment of celery extract produced dose-dependent reduction in all experimentally induced gastric lesions. Ethanol (80%) decreased the levels of GWM, NP-SH and increase in MDA concentration in gastric tissue. Celery extract showed the ability to significantly replenish the ethanol-induced depleted levels of GWM and gastric mucosal NP-SH. The gastric mucosal MDA level was also significantly lowered in extract pretreated rats. The celery extract showed stomach protection against the models used for ulcerogenesis. Results were further confirmed by using histopathological assessment. The phytochemical screening showed the presence of various chemical constituents such as flavonoids, tannins, volatile oils, alkaloids, sterols and/or triterpenes. Acute toxicity test revealed no deleterious or toxic symptoms or mortality over a period of 14 days. However, the LD50 was found to be 7.55 g/kg, and showed a large margin of safety. The results suggest that Apium graveolens extract significantly protects the gastric mucosa and suppresses the basal gastric secretion in rats, possibly through its antioxidant potential.

Novel flavonoids with antioxidant activity from a Chenopodiaceous plant

Objective: Atriplex lentiformis (Torr.) S.Wats (Chenopodiaceae) is a wild plant which is in use by Bedouin in treatment of general fatigue, therefore, there is a need to explore the potential antioxidant activity of the extracts and isolated compounds of this plant. Methods: Column chromatography and spectroscopic analysis were used for isolation and identification of the compounds. The antioxidant activity was evaluated in vitro using the ABTS•+ (2,2′-azino-bis-3-ethyl-bezthiazoine-6-sulphuric acid) radical scavenging model. Liver and kidney functions were investigated after oral administration of total alcohol, successive extracts, and isolated compounds. Results: Two new flavonoids, quercetin-6,4′-dimethoxy-3-fructo-rhamnoside 1 and quercetin-4′-methoxy-3-fructo-rhamnoside 2 in addition to five known compounds (kaempferol-4′-methoxy-3-rutinoside 3, kaempferol-7-O-rhamnoside 4, kaempferol-3,7-O,O-dirhamnoside 5, quercetin 6, and kaempferol 7) were isolated. Oral administration of total ethanol, diethyl ether, chloroform, ethyl acetate and n-butanol extracts showed no signs of toxicity up to (5 g/kg. b.wt.). All extracts and isolated compounds showed varied antioxidant activity ranged from 129 to 952 µmol Trolox equivalent/gram dry weight with maximum level for the two new isolated flavonoids (985 and 895 µmol Trolox equivalent/gram dry weight). Animals received both total ethanol and n-butanol extracts showed a significant increase in ALT, AST, blood urea, and serum creatinine levels.

Effect of Emex spinosa, Leptadenia pyrotechnica, Haloxylon salicornicum and Ochradenus baccatus extracts on the reproductive organs of adult male rats.

Context: Emex spinosa (L.) Campd. (Polygonaceae), Leptadenia pyrotechnica (Forsk.) Decne (Asclepiadaceae), Haloxylon salicornicum (Moq.) Bunge ex Bioss. (Chenopodiaceae) and Ochradenus baccatus Delile (Resedaceae) are used in folk medicine for treatment of male sexual disorders. Objective: To investigate the effects of E. spinosa, L. pyrotechnica, H. salicornicum and O. baccatus extracts on the reproductive system of male rats after prolonged period of treatment. Methods: Seventy-eight healthy adult male Wistar rats were divided into 13 groups (6 animals, each). The plant extracts (100, 200 and 400 mg/kg) were given daily by gavage to different groups of rats for 65 days. The thirteenth group (control) received the vehicle only. Test and control rats were mated with estrus female rats on days 30, 45 and 60 of treatment. Body and relative reproductive organ weights, and sperm parameters were recorded. Results: Animals treated with the ethanol extracts of E. spinosa and L. pyrotechnica showed significant improvement of the relative weight of reproductive organs, sperm count, sperm motility and total sperm abnormality. The mean sperm count for E. spinosa group (400 mg/kg) was 233.7 ± 4.50 × 106/mL, for L. pyrotechnica (200 and 400 mg/kg) groups were 237.0 ± 5.22 × 106/mL and 240.3 ± 4.64 × 106/mL, respectively and that of the control group was 218.1 ± 4.28 × 106/mL. The sperm motility of the control group was 77.5 ± 2.12, those of E. spinosa (400 mg/kg) group was 87.3 ± 3.50% and those of L. pyrotechnica (200 and 400 mg/kg) groups were 86.0 ± 3.11 and 89.7 ± 2.90%, respectively. Ethanol extracts of E. spinosa (400 mg/kg) and L. pyrotechnica (200 and 400 mg/kg) significantly elevate the serum levels of testosterone (5.30 ± 0.15, 5.32 ± 0.20 and 5.66 ± 0.19 ng/mL, respectively vs 4.64 ± 0.16 ng/mL) and luteinizing hormone (0.69 ± 0.03, 0.70 ± 0.03 and 0.74 ± 0.03 mIU/mL, respectively vs 0.59 ± 0.02 mIU/mL). On the other hand, no alterations were observed in body and relative organ weights, sperm numbers as well as sperm morphology of the male rats after the exposure to the H. salicornicum and O. baccatus extracts for 65 days. Conclusions: E. spinosa and L. pyrotechnica extracts appear to possess fertility improvement activity in male rats due to their testosterone increasing property. Moreover, the results suggest the absence of male reproductive toxicity of the H. salicornicum and O. baccatus extracts at tested doses.

Design and synthesis of some novel hydrazide, 1,2-dihydropyridine, chromene derivatives carrying biologically active sulfone moieties with potential anticancer activity.

This paper describes the synthesis of some novel sulfones having biologically active hydrazides (4-9, 22, 23, 26 and 27), hydrazonoyl cyanide (24), 1,2-dihydropyridines (16-21), chromene (28) and benzochromene (29) moieties starting with 1-[4-(piperidin-1-ylsulfonyl)phenyl]-ethanone 1. The structures of the the newly synthesized compounds were confirmed by elemental analysis, IR, 1H NMR and 13C NMR. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against breast cancer cell line (MCF7).