Crystal structures of three indole derivatives: 3-ethnyl-2-methyl-1-phenylsulfonyl-1H-indole, 4-phenylsulfonyl-3H,4H-cyclopenta[b]indol-1(2H)-one and 1-{2-[(E)-2-(5-chloro-2-nitrophenyl)ethenyl]-1-phenylsulfonyl-1H-indol-3-yl}ethan-1-one chloroform monosolvate

The title compounds, C17H13NO2S, (I), C17H13NO3S, (II), and C24H17ClN2O5S·CHCl3, (III), are indole derivatives. Compounds (I) and (II) crystalize with two independent molecules in the asymmetric unit. The indole ring systems in all three structures deviate only slightly from planarity, with dihedral angles between the planes of the pyrrole and benzene rings spanning the tight range 0.20 (9)–1.65 (9)°. These indole ring systems, in turn, are almost orthogonal to the phenylsulfonyl rings [range of dihedral angles between mean planes = 77.21 (8)–89.26 (8)°]. In the three compounds, the molecular structure is stabilized by intramolecular C—H...O hydrogen bonds, generating S(6) ring motifs with the sulfone O atom. In compounds (I) and (II), the two independent molecules are linked by C—H...O hydrogen bonds and C—H...π interactions, while in compound (III), the molecules are linked by C—H...O hydrogen bonds, generating R22(22) inversion dimers

Synthesis of Calothrixins and Its Analogs Using FeCl₃‑Mediated Domino Reaction Protocol

A novel one pot synthesis of calothrixin B and its analogs is achieved involving an FeCl₃-mediated domino reaction of enamines in dry DMF at reflux. Alternatively, the enamines upon interaction with CuBr₂ in DMF at reflux led to the formation of 1-phenylsulfony-2-(2′-nitroaryl)-4-hydroxycarbazole-3-carbaldehydes in excellent yields

Novel isothiacalothrixin B analogues exhibit cytotoxic activity on human colon cancer cells in vitro by inducing irreversible DNA damage.

Preliminary cytotoxic analysis of sulphur containing isosteric analogues of calothrixin B identified the useful anti-tumour activity of thia/isothiacalothrixin B which necessitated it's biological evaluation in colon and lung cancer cell lines. The isothia analogues induced cytotoxicity of HCT116 in a time-dependent manner and inhibited the clonogenic survival of HCT116 and NCI-H460 cells in a dose-dependent manner comparable to the standard anti-cancer drug camptothecin. Herein employing flow cytometry, we demonstrate that isothiacalothrixin B analogues inhibited proliferation of colon cancer cells by the arrest of cells in S and G2/M phases over a period of 48 hours at a concentration of 5 μM. Our results also suggest that the cytotoxicity of thia analogues of calothrixin B is partially mediated by induction of cellular DNA strand breaks. The UV-Vis spectroscopic studies with CT-DNA revealed groove binding for calothrixin B and its thia analogues wherein subsequent in silico molecular modelling studies indicated preferential binding to the AT-rich regions of minor groove of DNA. Furthermore, thiacalothrixin B caused transcriptional activation of p21waf1/cip1 promoter and upregulation of its protein levels independent of p53. The induction of DNA damage response pathway leads to apoptosis in isothiacalothrixin B but not in thiacalothrixin B treated cells. The isothia analogues SCAB 4 induced DNA strand breaks and cell cycle arrest even after treatment for a short period (i.e., 4 hours) and the cell cycle effects were irreversible. For the first time, this study provides detailed cellular effects on the potential use of isothiacalothrixin B analogues as cytotoxic agents

2-(4-Chloro-2-nitrophenyl)-9-phenylsulfonyl-9H-carbazole-3-carbaldehyde

In the title compound, C25H15ClN2O6S, the carbazole ring system is essentially planar, with a maximum deviation of 0.152 (3) Å for the C atom to which the 4-chloro-2-nitrophenyl ring is attached. Its mean plane is almost orthogonal to the phenylsulfonyl and nitrophenyl rings, making dihedral angles of 82.64 (14) and 79.89 (13)°, respectively. The N atom of the nitro group deviates by 0.032 (3) Å from the benzene ring to which it is attached. The molecular structure features intramolecular O—H...O and C—H...O hydrogen bonds, which generate three S(6) ring motifs. In the crystal, molecules are linked by C—H...O hydrogen bonds, which generate C(6) and C(9) chains running in the [100] and [010] directions, respectively, forming a two-dimensional network lying parallel to (001). There are also R43(28) supramolecular graph-set ring motifs enclosed within these networks

Synthesis and Biological Evaluation of Calothrixins B and their Deoxygenated Analogues

A series of calothrixin B (<b>2</b>) analogues bearing substituents at the ‘E’ ring and their corresponding deoxygenated quinocarbazoles lacking quinone unit were synthesized. The cytotoxicities of calothrixins <b>1</b>, <b>2</b>, and <b>15b</b>–<b>p</b> and quinocarbazole analogues were investigated against nine cancer cell lines. The quinocarbazoles <b>21a</b> and <b>25a</b> inhibited the catalytic activity of human topoisomerase II. The plasmid DNA cleavage abilities of calothrixins <b>1</b>, <b>2</b>, and <b>15b</b>–<b>p</b> identified compound <b>15h</b> causing DNA cleavage comparable to that of calothrixin A (<b>1</b>). Calothrixin A (<b>1</b>), 3-fluorocalothrixin <b>15h</b> and 4-fluoroquinocarbazole <b>21b</b> induced extensive DNA damage followed by apoptotic cell death. Spectral and plasmid unwinding studies demonstrated an intercalative mode of binding for quinocarbazoles. We identified two promising drug candidates, the 3-fluorocalothrixin B <b>15h</b> with low toxicity in animal model and its deoxygenated derivative 4-fluoroquinocarbazole <b>21b</b> as having potent cytotoxicity against NCI-H460 cell line with a GI₅₀ of 1 nM