Reddymasu Sreenivasulu

Synthesis, cytotoxic activity and docking studies of new 4-aza-podophyllotoxin derivatives

Abstract The synthesized nine aza-podophyllotoxin derivatives (8a–f, 10, 12and14) have been evaluated for their cytotoxicity in a panel of tumor cancer cell lines (Zr-75-1, MCF7, KB, Gurav, DWD, Colo-205, A-549 and Hop62). Among them, 8a and 8b compounds show stronger growth inhibition activity than the standard drug etoposide. Further, molecular docking simulations were carried out against human topoisomerase II, a putative target for these classes of molecules.

A concise stereoselective total synthesis of (−)-cephalosporolide D

A concise stereoselective total synthesis of eight-membered lactone (−)-cephalosporolide D has been derived from inexpensive and commercially available starting material (S)-propylene epoxide. This concise synthesis utilizes Grignard reaction, Noyori asymmetric reduction, and Yamaguchi macrolactonization as key steps.Graphical abstract

A concise stereoselective total synthesis of diplodialide C

An asymmetric total synthesis of diplodialide C has been achieved starting from commercially available homoallylic alcohol. Regioselective opening of the chiral epoxide, cross-metathesis reaction, and Yamaguchi macrolactonization were used as the key steps in this synthesis.Graphical Abstract

Synthesis of chalcone incorporated quinazoline derivatives as anticancer agents

A series of ten novel chalcone incorporated quinazoline derivatives (11a–11j) were designed and synthesized. All the synthesized compounds were evaluated for their anticancer activities against four human cancer cell lines (A549, HT-29, MCF-7 and A375). Among them, four compounds, 11f, 11g, 11i and 11j showed more potent anticancer activity than the control drug, Combretastatin – A4.

Synthesis and biological evaluation of benzoxazole fused combretastatin derivatives as anticancer agents

A series of ten novel benzoxazole analogues of combretastatin A-4 were designed, synthesized, and evaluated for their anticancer activity against three human cancer cell lines. Four of the synthesized compounds exhibited superior potency against different tumour cell lines. One of them showed more potent than control drug, particularly A549 and MCF-7 cell lines.Graphical abstract

Stereoselective total synthesis of (−)-(5S,8R,13S,16R)-pyrenophorol

The total synthesis of 16-membered C2-symmetric dilactone (−)-(5S,8R,13S,16R)-pyrenophorol was accomplished starting from enantiomerically pure propylene oxide prepared by hydrolytic kinetic resolution of (±)-propylene oxide with key steps of cross-metathesis and intermolecular Mitsunobu cyclization for the construction of macrolactone.Graphical abstract

Stereoselective total synthesis of verbalactone

Abstract A simple and efficient route for the stereoselective total synthesis of verbalactone from commercially available inexpensive starting material d-mannitol using Barbier allylation, α-aminoxylation, and Yamaguchi macrolactonization as key steps is reported.Graphical Abstract

Stereoselective synthesis of (−)-tetrahydropyrenophorol

A simple and efficient synthesis of macrocyclic dilactone tetrahydropyrenophorol has been accomplished from inexpensive and commercially available starting materials. This concise synthesis utilizes regioselective ring opening of epoxide, asymmetric dihydroxylation, and Mitsunobu reaction for the construction of the macrolactone.Graphical abstract

Design and synthesis of new 2,5-disubstituted-1,3,4-oxadiazole analogues as anticancer agents

In continuance of our search for new anticancer agents, we report herein the design, synthesis, and anticancer evaluation of oxadiazole analogues. Two series (4a-h and 4i-q) of new oxadiazole analogues were designed based on heterocyclic (1,3,4-oxadiazole)-linked aryl core of IMC-038525 (tubulin polymerization inhibitor), NSC 776715, and NSC 776715 and synthesized. All the compounds were fully characterized by infrared, nuclear magnetic resonance spectroscopy, and mass spectral data and the purity of compounds was checked by elemental analysis (C, H, and N analysis). Further seven compounds were evaluated for anticancer activity on nine different panels of 60 cell lines (60 NCI cancer cell lines) according to the National Cancer Institute screening protocol and percent growth and percent growth inhibition was calculated at 10 µM drug concentration. Ten compounds were evaluated for anticancer activity on two cancer cell lines (HeLa and MDA-MB-435) as per the standard protocol reported at four different drug concentrations (10−7, 10−6, 10−5, and 10−4 µM) and GI50, LC50, and TGI dose-related parameters were calculated. The compound 4j showed maximum anticancer activity at 10 µM, and was found to have higher sensitivity against MOLT-4, IGROV1, HCT-116, and K-562 with percent growth inhibitions of 50.38, 48.45, 46.26, and 46.26 respectively. The compound 4j showed superior anticancer activity than imatinib on 41 human cancer cell lines. The compound 4p showed anticancer activity with GI50 of 36.7 and 46.5 µM against HeLa and MDA-MB-435 cell lines, respectively.