K. Srinivasa Reddy

Synthesis, DNA-binding ability and anticancer activity of benzothiazole/benzoxazole-pyrrolo[2,1-c][1,4]benzodiazepine conjugates

A series of benzothiazole and benzoxazole linked pyrrolobenzodiazepine conjugates attached through different alkane or alkylamide spacers was prepared. Their anticancer activity, DNA thermal denaturation studies, restriction endonuclease digestion assay and flow cytometric analysis in human melanoma cell line (A375) were investigated. One of the compounds of the series 17d showed significant anticancer activity with promising DNA-binding ability and apoptosis caused G0/G1 phase arrest at sub-micromolar concentrations. To ascertain the binding mode and understand the structural requirement of DNA binding interaction, molecular docking studies using GOLD program and more rigorous 2 ns molecular dynamic simulations using Molecular Mechanics-Poisson-Boltzman Surface Area (MM-PBSA) approach including the explicit solvent were carried out. Further, the compound 17d was evaluated for in vivo efficacy studies in human colon cancer HT29 xenograft mice.

Imino Diels–Alder Reactions: Efficient Synthesis of Pyrano and Furoquinolines Catalyzed by ZrCl4

Abstract Anhydrous zirconium tetrachloride is found to be an efficient catalyst for the Imino Diels–Alder reactions of N‐benzylideneanilines with 3,4‐dihydro‐2H‐pyran and 2,3‐dihydrofuran to afford pyrano and furo [3,2‐c] quinolines in good yields.

An efficient synthesis of bis(indolyl)methanes and evaluation of their antimicrobial activities

A versatile and efficient method has been developed for the synthesis of bis(indolyl)methanes by using aluminium triflate (0.5 mol%) as a novel catalyst. Further, some of the synthesized compounds were evaluated for their efficacy as antibacterial and antifungal activities. Most of the compounds have shown moderate to good inhibitory activity.

Synthesis, DNA-binding ability and evaluation of antitumour activity of triazolo[1,2,4]benzothiadiazine linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates.

A series of triazolobenzothiadiazine-pyrrolobenzodiazepine conjugates linked through different alkane spacers have been prepared. These compounds have exhibited significant cytotoxicity against most of the cell lines examined. Compound 5a displays GI(50) values from 1.83 to 2.38 microM against seven human tumour cell lines, and is identified as a promising lead compound from this series. Their DNA thermal denaturation studies have also been carried out, and one of the compounds 5c elevates the DNA helix melting temperature of the CT-DNA by 2.6 degrees C after incubation for 36 h.

Synthesis, Structural Characterization and Biological Evaluation of Novel [1,2,4]triazolo [1,5‐b][1,2,4]benzothiadiazine‐benzothiazole Conjugates as Potential Anticancer Agents

Two series of 10‐substituted 5,5‐dioxo‐5,10‐dihydro[1,2,4]triazolo[1,5‐b][1,2,4]benzothiadiazine 2‐methyl/ethyl sulfanyl benzothiazole derivatives (5a–d) and 10‐substituted 5,5‐dioxo‐5,10‐dihydro[1,2,4]triazolo[1,5‐b][1,2,4] benzothiadiazine 2‐phenoxy benzothiazole derivatives (16a–c) were synthesized and their structures confirmed by NMR, MS, IR and X‐ray crystallography. These compounds were evaluated for their cytotoxicity against 60 human tumour cell lines. One of the synthesized compounds (5b) exhibited significant inhibitory activity against most of the cell lines and has been further evaluated for the five‐dose screening.

Ultrasound-accelerated synthesis of chiral allylic alcohols promoted by indium metal

The 2-iodomethyl-O-isopropylidine acetals undergo smoothly β-elimination by indium metal in methanol under sonication to afford the corresponding allylic alcohols in excellent yields with high selectivity. This method tolerates both acid and base labile functional and protecting groups and also free hydroxyl groups present in the molecule. Improved yields and enhanced rates are the remarkable features obtained by ultrasound.

Indium-mediated facile cleavage of the t-butoxycarbonyl group from di-t-butylimidodicarbonate

Di-t-butylimidodicarbonates are selectively and efficiently deprotected to the corresponding mono-BOC protected amines in high yields using indium or zinc metal in refluxing methanol. Simple BOC and CBz protected amines are unaffected by these conditions.

Carbazole–pyrrolo[2,1-c][1,4]benzodiazepine conjugates: design, synthesis, and biological evaluation

A series of carbazole–pyrrolobenzodiazepine conjugates (4a–g and 5a–f) have been designed, and synthesized as anticancer agents. These compounds are prepared by linking the C8-position of DC-81 with a carbazole moiety through simple alkane spacers as well as piperazine side-armed alkane spacers in good yields. The DNA binding ability of these conjugates has been determined by thermal denaturation studies and also supported by molecular docking studies. These conjugates showed potent anticancer activity with GI50 ranging from 5.27–0.01 μM. The FACS analysis and BrdU assay of selected conjugates (4c, 4f, 5a and 5f) on MCF-7 cell lines disclosed the increased G1 cell cycle arrest and one of the conjugates 5f has exhibited significant anticancer activity. The analysis of the intrinsic factors involved in causing the G1 arrest in MCF-7 cell lines by 5f conjugate has been demonstrated on the proteins which play a vital role in G1 arrest followed by apoptosis (Cyclin D1, CDK4, c-Jun, JunB, CREB, p53, JNK1/2, procaspase-7, cleaved PARP, pRb, and BAX). Thus, these PBD conjugates (in particular 5f) have promising potency for combating human carcinoma.

Addition of carbon nucleophiles to aldehyde tosylhydrazones of aromatic and heteroaromatic-compounds: total synthesis of piperine and its analogs

Addition of carbon nucleophiles to aldehyde tosylhydrazones of aromatic and heteroaromatic compounds is reported. New observations have been made wherein alkylative reduction is observed in some cases whereas alkylative fragmentation is noticed in others. These findings are exploited in the synthesis of the useful alkaloid piperine and its analogs.