A research are related to the synthesis, investigation, and analytical application of phthalexons was developed at Saratov State Pedagogical Institute under the direction of Prof. Cherkasov [1]. Phthalexons are compounds of the triphenylmethane series whose molecules involve iminodiacetate fragments. A specific feature of the structure of sulfophthalexons is that they can exist both as inner complex salts (zwitterions) (A) and as the form with the closed heterocycle (B).The aim of this work was to solve the problem of revealing the structure of sulfophthalexon molecules using quantum-chemical methods. The compounds under study were phthalexon S ( I ), ortho -chlorophthalexon S ( II ), ortho -bromorophthalexon S ( III ), orthocresolphthalexon S (Xylenol Orange) ( IV ), para-xylenolphthalexon S ( V ), thymolphthalexon S (Methylthymol Blue) ( VI ), and meta -cresolphthalexon S ( VII ). EXPERIMENTALCalculations were performed by the PM3 method [2] using the HyperChem program (HyperChem (TM), HyperCube Inc., 1115 NW 4th Street, Gainesville, Florida 32601, USA) with full geometry optimization (Polak-Ribiere procedure [3]). In quantum-chemical calculations, the gradient norm was no higher than 0.02 kcal mol -1 Å -1 for isolated phthalexon molecules and 1 kcal mol -1 Å -1 for supermolecular systems containing water. For clusters involving 197 water molecules, the minimum distance between the molecules of water and the dissolved compound was 1.7 Å. C Y OH CH 2 N(CH 2 COOH) 2 X X (HOOCCH 2 ) 2 NCH 2 HO Y Z Z SO 3 + -C Y OH CH 2 N(CH 2 COOH) 2 X X (HOOCCH 2 ) 2 NCH 2 HO Y Z Z SO 2 O A B ARTICLESAbstract -On the basis of quantum-chemical calculations, it is demonstrated that, for isolated sulfophthalexon molecules, the heterocyclic form is thermodynamically more stable than the open zwitterionic form. On the contrary, the latter is predominant in aqueous solutions.

Since cancer remains one of the most prevalent diseases today, there is an urgent need for the development of new agents. Triterpenoids may act in multiple pathways displaying antiproliferative, antiangiogenic, anti-inflammatory, and pro-apoptotic activities that place them as promising multifunctional agents in treating cancer. In this paper a series of betulonic acid and its N-methylpyperazinyl amide derivatives, especially holding C2-nicotinoylidene/furfurylidene/fluorobenzylidene fragments, have been synthesized and evaluated for their cytotoxic activity against the NCI-60 cancer cell line panel. N-Methylpiperazinyl amides of betulinic acid 11 and 4-pyridinoylidene-betulinic acid 9 as well as betulonic acid C2-4-pyridinoylidene- 14 or furfurylidene 16 derivatives were found to be the leading compounds with GI50 values of 0.49 μM for leukemia CCRF-CEM, 1.60 μM and 1.36 μM for colon cancer HCT-116 and 1.66 μM for melanoma LOX IMVI cell lines, respectively. The activity displayed for these compounds was higher than for the standard drug doxorubicin against colon cancer HCT-15 and ovarian cancer NCI/ADR-RES cell lines. Cell cycle analysis indicates that compound 11 promotes cytotoxic activity through the apoptosis induction both in conditionally normal (HEK293) and in cancer (A549, MCF-7) cells, whereas compound 14 exhibits both cytostatic and cytotoxic activity, dependently on cell line evaluated. In particular, in HEK293 cells the compound 14 induces mainly apoptotic cell death, while in A549 and MCF-7 cells cytostatic effect is dependent on cell cycle arrest in G2/M phase.Our results suggest that betulinic acid N-methylpyperazinyl amide 11 is the promising compound for the future drug development antitumor studies.