We report on the synthesis and biological evaluation of two series of 2,4,5-polysubstituted thiazoles comprising the acid hydrazide functionality and some derived pharmacophores known to contribute to various chemotherapeutic activities. All newly synthesized compounds were subjected to in-vitro antibacterial and antifungal screening. Of the compounds tested, 13 derivatives displayed inhibitory effect on the growth of three Gram-positive strains while they lack activity against Gram-negative bacteria. Moreover, four compounds were able to exert antifungal activity against C. albicans. Potential antibacterial and antifungal activities were linked to the thiosemicarbazide function 6a-f and those substituted with both the thioureido and thiosemicarbazide moieties 12a-f. Compounds 6f and 12f (R = 4-F-C(6)H(4)) could be considered as the most active members in this investigation with a broad spectrum of antibacterial activity against three types of Gram-positive bacteria, together with an appreciable antifungal activity against C. albicans. Compounds 6d, 6f, and 12f were twice as active as ampicillin against B. subtilis. The best antifungal activity was shown by compound 6d 50% less active than clotrimazole. 17 compounds were selected and tested for their preliminary in-vitro anticancer activity according to the current one-dose protocol of the NCI. Three cell lines, non-small cell lung cancer Hop-92, ovarian cancer IGROV1, and melanoma SK-MEL-2, exhibited some sensitivity against most of the tested compounds. Compound 12f proved to be the most active anticancer member with a broad spectrum of activity against most of the tested subpanel tumor cell lines. Consequently, 12f was carried over to be tested in the five-dose assay.

The synthesis of some new 3-cyano-1,4, 6-trisubstituted-2(1H)-pyridinones supported with various pharmacophores and functionalities at positin-1 is described. The in vitro anticancer activity of 24 of the newly synthesized compounds was evaluated according to the protocol of the NCI in vitro disease-oriented human cells screening panel assay. The results revealed that five compounds 4a-c, 7b, and 12b were able to display moderate antitumor potential against some of the tested subpanel tumor cell lines at the GI 50 and TGI levels, however, with marginal or no cytotoxic (LC 50 ) activity. The obtained data suggested that better antitumor activity was linked to derivatives with either 4-bromophenyl or 3,4-dimethoxyphenyl moieties, together with a 1-methyl-1H-pyrrol-2-yl counter part at positions 6 and 4, respectively. Consequently, the 3-cyano-4-(1-methyl-1H-pyrrol-2-yl)-6-(4-bromophenyl or 3,4-dimethoxyphenyl)-2(1H)-pyridinones 4a and 4b, could be considered as the most active members identified in this investigation as evidenced from their relative higher growth inhibitory (GI 50 (MG-MID) 77.6 and 67.6 lM, respectively) and cytostatic (TGI (MG-MID) 85.1 and 95.5 lM, respectively) activities, when compared with the substituted thiocarbamoyl analog 7b and the bicyclic [1,2,4]triazolo[3,4-a]pyridine derivative 12b.

Some new benzenesulfonamides, disubstituted sulfonylureas, and sulfonylthioureas substituted basically with 3-(2-thienyl or 3-pyridyl)-indeno [1,2-c]pyrazol(in)e counterpart were synthesized to be evaluated for their in vitro antitumor activity. Some of the thioureido derivatives were cyclized to the corresponding five-membered thiazolidinons, thiazolines, and the six-membered thiazinones as interesting structure variants. According to the protocol of the National Cancer Institute (NCI) in vitro disease-oriented human cells screening panel assay, 13 compounds showed promising broad spectrum antitumor activity. In general, compounds containing the thienyl moiety displayed better antitumor spectra than those containing the pyridyl moiety. Compound 5, 4-(3-(2-thienyl)-3H-indeno[1,2-c]pyrazol-2-yl)-benzenesulfonamide [GI 50 , TGI, and LC 50 (MG-MID) values of 13.2, 33.1 and 69.2 lM, respectively] proved to be the most active member in this study with variable degrees of potencies against all the tested subpanel tumor cell lines and particular effectiveness against the leukemia and prostate subpanels at both the GI 50 (3.30 and 8.68 lM, respectively) and the TGI levels (15.7 and 22.3 lM, respectively).The wide spread of cancer in recent years has prompted the search for new therapeutic agents in this field. As part of our ongoing program aimed towards the development of new potential chemotherapeutic agents (Fahmy et al.

This research work describes the synthesis and biological properties of some novel polysubstituted fused heterocyclic ring systems namely; pyrano[4,3-c] pyrazoles and pyrazolo [4,3c]pyridines. Such targeted compounds where designed so as to hybridize the pyrazole ring with the pyrone and/or pyridine moieties, respectively, hoping to obtain synergistic anticancer and/or antimicrobial activities. The chemistry of the reactions employed in the synthesis of the target compounds together with their chemical behaviour, are discussed and the structures of the newly synthesized compounds were confirmed by the IR and 1 H-NMR spectral data. All the synthesized compounds showed weak anticancer activity according to the protocol of the National Cancer Institute (NCI), Maryland, USA. Additionally, they showed weak antimicrobial activity against some bacteria and fungi.

Condensation of cyclic ketones J. with ethänolamines gave the corresponding spiro-oxazolidines 2. The thioamides 3 were obtained in good yields through reaction of 2 with the appropriate isothiocyanate. Reaction of 2 with formaldehyde or acetaldehyde in the presence of the appropriate amine afforded the corresponding aminomethyl spiro-compounds 4 and 5 respectively, in excellent yields. The structures of the isolated compounds were fully determined by spectral methods. Antimicrobial activities of some oxazolidines were also discussed.