Solvent-free synthesis and anticancer activity evaluation of benzimidazole and perimidine derivatives.

Benzimidazoles and perimidines are subsidiary structures for research and development of new biologically active molecules and have established prominence because of their promising biological activities. Two series of diversified heterocyclic molecules, tetracyclic benzimidazole derivatives, tetracyclic and pentacyclic perimidine derivatives have been synthesized in good yields by condensation of acid anhydrides and diacids with various diamines using microwave irradiation. All synthesized derivatives were fully characterized and evaluated for in vitro antiproliferative activity against five human cancer cell lines. Compounds 3a (breast T47D, lung NCl H-522), 3b (colon HCT-15), 3d (lung NCl H-522, ovary PA-1), 3f (breast T47D, liver HepG2) and 5a (breast T47D) exhibited good anticancer activity with [Formula: see text] values ranging from [Formula: see text] to [Formula: see text].

Solvent free, catalyst free, microwave or grinding assisted synthesis of bis-cyclic imide derivatives and their evaluation for anticancer activity.

Cyclic imides are well known to be very important antitumor agents such as mitonafide and amonafide etc. Based on this fact, we have synthesized two series of cyclic imide derivatives containing two cyclic imide moiety in their structures (bis-cyclic imides) and screened them for in vitro anticancer activity against five human cancer cell lines i.e. breast (T47D), lung (NCl H-522), colon (HCT-15), ovary (PA-1) and liver (Hep G2). One series of bis-cyclic imide derivatives (3a-h) have been synthesized by condensation of acid anhydrides (1a-b) with diamines (2a-d) and another series (9a-f, 10a-f, 11a-f and 12a-f) by condensation of various diamines (4a-f) with diacids (5-8) in good yields. Structures assigned to 3a-h, 9a-f, 10a-f, 11a-f and 12a-f were fully characterized by spectroscopic means and elemental analysis. On screening for in vitro anticancer activity, compounds 3a (breast T47D), 3d (breast T47D, liver Hep G2), 3e (breast T47D, liver Hep G2), 3h (colon HCT-15), 10f (liver Hep G2) and 11a (colon HCT-15, ovary PA-1) exhibited good anticancer activities with IC50 values range from 12.41±3.2 to 17.9±2.5µM.

Synthesis of amidine and bis amidine derivatives and their evaluation for anti-inflammatory and anticancer activity.

2-Cyanopyridine (1a), 4-cyanopyridine (1b), 2-cyanopyrazine (1c) on condensation with mono amines (2a-c) and diamines (4a-c) in the presence of sodium methoxide as catalyst gave amidine derivatives (3a-i) and bis amidine derivatives (5a-i) in good yields. All these compounds were fully characterized by spectroscopic means and elemental analysis. On screening for anti-inflammatory activity and for in vitro anticancer activity compounds 5c and 5d exhibited good anti-inflammatory activity whereas compounds 5d breast (T47D), 5h, 5i lung (NCI H-522), 5i colon (HCT-15), 3c, 3h, 5i ovary (PA-1) and 3c, 5b, 5h liver (HepG2) exhibited good anticancer activity.

Synthetic DNA minor groove-binding drugs.

In this review, both cationic and neutral synthetic ligands that bind in the minor groove of DNA are discussed. Certain bis-distamycins and related lexitropsins show activities against human immunodeficiency virus (HIV)-1 and HIV-2 at low nanomolar concentrations. DAPI binds strongly to AT-containing polymers and is located in the minor groove of DNA. DAPI intercalates in DNA sequences that do not contain at least three consecutive AT bp. Berenil can also exhibit intercalative, as well as minor groove binding, properties depending on sequence. Furan-containing analogues of berenil play an important role in their activities against Pneumocystis carinii and Cryptosporidium parvuam infections in vivo. Pt(II)-berenil conjugates show a good activity profile against HL60 and U-937 human leukemic cells. Pt-pentamidine shows higher antiproliferative activity against small cell lung, non-small cell lung, and melanoma cancer cell lines compared with many other tumor cell lines. trans-Butenamidine shows good anti-P. carinii activity in rats. Pentamidine is used against P. carinii pneumonia in individuals infected with HIV who are at high risk from this infection. A comparison of the cytotoxic potencies of adozelesin, bizelesin, carzelesin, cisplatin, and doxorubicin indicates that adozelesin is a potent analog of CC-1065. Naturally occurring pyrrolo[2,1-c][l,4]benzodiazepines such as anthramycin have a 2- to 3-bp sequence specificity, but a synthetic PBD dimer spans 6 bp, actively recognizing a central 5'-GATC sequence. The crosslinking efficiency of PBD dimers is much greater than that of other major groove crosslinkers, such as cisplatin, melphalan, etc. Neothramycin is used clinically for the treatment of superficial carcinoma of the bladder.

Extraction and spectrophotometric determination of Pd(II) with 3,4,4a,5-tetrahydro-3,3,4a-trimethyl-7-(substituted)-pyrimido(1,6-a)-benzimidazole-1-thiol (PBT).

A method for the extraction-spectrophotometric determination of palladium with 3,4,4a,5-tetrahydro-3,3,4a-trimethyl-7-(substituted)-pyrimido(1,6-a)benzimidazole-1-thiol (PBT) is described. PBT-Pd(II) complex is extracted from an acidic aqueous solution (0.01-0.5M HClO(4)) into a chloroform layer. The absorbance is measured at 438 nm and the molar absorptivity found to be 1.033 x 10(4)M(-1) cm(-1). The complex system conforms to Beer's law over the range 1.9-28.5 mug/ml palladium(II). The effects of pH (2-6), HClO(4) concentration, PBT concentration and shaking time were studied. The ratio of metal ion to ligand molecules in the coloured complex was found to be 1:4. The tolerance limit for many metals have been determined. Finally, the method has been applied successfully to the determination of palladium in synthetic mixtures and in the standard palladium carbon powder (palladium catalyst).

10-Acetyl-10-hydroxyxantho[2,3-f]tetralin 8-glycosides as angular chromophore analogues of anthracyclines: synthesis, redox properties, microsomal oxygen consumption, and antileukemic evaluation.

10-Acetyl-7,8-dihydroxyxantho[2,3-f]tetralin is obtained by photo-Fries rearrangement of an acylated and double ketal protected tetralin followed by sodium thiocresylate catalyzed rearrangement of the resulting benzoyltetralin. Introduction of the 10-hydroxy function with base, triethyl phosphite, and molecular oxygen affords six products. These include the desired epimeric 10-acetyl-7,8,10-trihydroxyxantho[2,3-f]tetralins in addition to products resulting from novel valence tautomerism and cycloreversion reactions in the oxidation reaction. Glycosidic coupling to the fully functionalized cis-8,10-dihydroxy epimer of the aglycon to protected chlorodaunosamine by a modified Koenigs-Knorr method proceeded satisfactorily. By contrast the epimeric trans-8,10-dihydroxy compound failed to undergo coupling under these conditions. This is attributed to facile competing intramolecular hemiketal formation in the latter case. The new angular glycosides are very resistant to electrochemical reduction and display very low (3-10%) augmentation of hepatic microsomal oxygen consumption relative to doxorubicin. The observed, albeit low, cytotoxicity against leukemia L1210 in cell culture provides an additional example where the presence of the quinone moiety in the parent anthracyclines, which is implicated in the clinical cardiotoxicity, may not be necessary for the expression of anticancer properties.

Deoxyribonucleic acid cleavage specificity of a series of acridine- and acodazole-iron porphyrins as functional bleomycin models.

A series of metalloporphyrins linked through basic chains to certain DNA interactive groups has been synthesized. Several of these agents reproduce the characteristic properties of the antitumor glycopeptide bleomycin, including the oxygen-mediated scission of DNA in the presence of thiols, antibiobic activity under aerobic conditions, and activity against human and animal tumor models. Initial screening by scission of PM2-CCC-DNA identified six of the compounds, including those bearing acridine and acodazole intercalating groups, as the most active. The specificity of the oxygen-mediated scission of a 139 base pair HindIII/NciI restriction fragment of pBR322 by these six selected agents was then determined and compared with the action of pancreatic DNase by densitometric scans. All six of these compounds produce uniform base and sequence neutral cleavage of the restriction fragment at each base site. The six active compounds bear either of two types of intercalators, 6-chloro-2-methoxyacridine or acodazole, and with linkages to the ferric binding domain of -NH(CH2)2-, -NH(CH2)3-, -NH(CH2)4-, or -NH(CH2)3NH(CH2)3- and either porphyrin or deuteroporphyrin moieties. Comparison of the Kassoc values for binding to calf thymus DNA suggests that the enhanced binding observed with the linker -NH(CH2)3NH(CH2)3- contributes to the efficiency of sequence neutral DNA scission and may be a factor in the relative anticancer activities of these agents. The iron porphyrins give no evidence of the production of base propenals in DNA degradation, and the autoradiograms clearly indicate that a phosphate group is attached to the 5' end of the oligomer. The scission is partially suppressible by catalase and superoxide dismutase.(ABSTRACT TRUNCATED AT 250 WORDS)