Synthesis and biological evaluation of novel tamoxifen-1,2,4-triazole conjugates.
A new class of compounds, structurally related to the breast cancer drug tamoxifen, was designed and synthesized. The McMurry coupling reaction was used as the key synthetic step in the preparation of these analogs, and the structural assignments were made on the basis of [Formula: see text] NMR, [Formula: see text] NMR, and HRMS studies. The absolute stereochemistry of E and Z isomers was unambiguously confirmed by a single-crystal X-ray diffraction analysis. Water was found to be an inexpensive nontoxic and effective medium for the C-N bond formation. Utilizing this protocol, various tamoxifen derivatives were synthesized in good yields. Environmental acceptability, low cost, and high yields are the important features of this protocol. These compounds were evaluated for their antiproliferative activity on five human tumor cell lines. Compound 4p ([Formula: see text]) showed improved antiproliferative activity against breast cancer cell line (MDA-MB-231) compared to tamoxifen ([Formula: see text]), while the compound 4o ([Formula: see text]) exhibited similar activity against SiHa compared to the reference drug, tamoxifen ([Formula: see text]). In addition, these analogs were investigated for their antibacterial activity against six bacterial strains. Preliminary results indicate that some of the newly synthesized title compounds exhibited promising antibacterial activity compared with the standard drug, vancomycin. A new class of compounds were designed rationally by the replacement of a ethyl group in tamoxifen with a methylene (1H-1,2,4-triazole) group. The absolute stereochemistry of E and Z isomers were unambiguously confirmed by a single-crystal X-ray diffraction analysis. The title compounds were evaluated for their antiproliferative and antibacterial activities.
Medicinal Chemistry & Pharmacology Division, Discovery Laboratory, CSIR-Indian Institute of Chemical Technology, Hyderabad, India. msrmurty@ymail.com.
M S R
MS
Murty
Medicinal Chemistry & Pharmacology Division, Discovery Laboratory, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Mohana Rao
MR
Katiki
Centre for X-Ray Crystallography, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Jagadeesh Babu
JB
Nanubolu
Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Srujana
S
Garimella
Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Sowjanya
S
Polepalli
Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Nishant
N
Jain
Bioengineering & Environmental Sciences, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Sudheer Kumar
SK
Buddana
Bioengineering & Environmental Sciences, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
R S
RS
Prakasham
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D005260:Female; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013237:Stereoisomerism; D013629:Tamoxifen / Q000031:analogs & derivatives*; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D014230:Triazoles; D013629:Tamoxifen
124-Triazole; Antibacterial; McMurry coupling; Piperazines; Tamoxifen