TY - JOUR
T1 - Synthesis of indole-tethered [1,3,4]thiadiazolo and [1,3,4]oxadiazolo[3,2-a]pyrimidin-5-one hybrids as anti-pancreatic cancer agents
AU - Gummidi, Lalitha
AU - Kerru, Nagaraju
AU - Awolade, Paul
AU - Raza, Asif
AU - Sharma, Arun K.
AU - Singh, Parvesh
N1 - Funding Information:
PS thanks to the National Research Foundation (NRF) South Africa for a Competitive Grant for unrated Researchers (Grant No. 121276). The author (GL) also thank the National Research Foundation (NRF) South Africa for the financial support toward the research efforts (NRF-TWAS UID: 110887). AKS thanks the Organic Synthesis Shared Resource of Penn State Cancer Institute and Department of Pharmacology, Penn State College of Medicine for financial support.
Funding Information:
PS thanks to the National Research Foundation (NRF) South Africa for a Competitive Grant for unrated Researchers (Grant No. 121276). The author (GL) also thank the National Research Foundation (NRF) South Africa for the financial support toward the research efforts (NRF-TWAS UID: 110887). AKS thanks the Organic Synthesis Shared Resource of Penn State Cancer Institute and Department of Pharmacology, Penn State College of Medicine for financial support.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/11/15
Y1 - 2020/11/15
N2 - New indole-tethered [1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one (8a-j) and [1,3,4]oxadiazolo[3,2-a]pyrimidin-5-one hybrids (9a-e) were synthesized using [4+2] cycloaddition reactions of functionalized 1,3-diazabuta-1,3-dienes with indole-ketenes. All molecular hybrids were structurally characterized by spectroscopic techniques (IR, NMR, and HRMS) and screened for their anti-pancreatic cancer activity in vitro. The [1,3,4]oxadiazolo[3,2-a]pyrimidin-5-one hybrids (9a-e) showed stronger anti-pancreatic cancer activity than the [1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one hybrids (8a-j) against the PANC-1 cell line. Compound 9d bearing an ortho-chlorophenyl moiety emerged as the most potent anti-pancreatic cancer agent with an IC50 value of 7.7 ± 0.4 µM, much superior to the standard drug Gemcitabine (IC50 > 500 µM). The discovery of these [1,3,4]thiadiazolo and [1,3,4]oxadiazolo[3,2-a]pyrimidin-5-one hybrids elicits their potentials as pursuable candidates for pancreatic cancer chemotherapy.
AB - New indole-tethered [1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one (8a-j) and [1,3,4]oxadiazolo[3,2-a]pyrimidin-5-one hybrids (9a-e) were synthesized using [4+2] cycloaddition reactions of functionalized 1,3-diazabuta-1,3-dienes with indole-ketenes. All molecular hybrids were structurally characterized by spectroscopic techniques (IR, NMR, and HRMS) and screened for their anti-pancreatic cancer activity in vitro. The [1,3,4]oxadiazolo[3,2-a]pyrimidin-5-one hybrids (9a-e) showed stronger anti-pancreatic cancer activity than the [1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one hybrids (8a-j) against the PANC-1 cell line. Compound 9d bearing an ortho-chlorophenyl moiety emerged as the most potent anti-pancreatic cancer agent with an IC50 value of 7.7 ± 0.4 µM, much superior to the standard drug Gemcitabine (IC50 > 500 µM). The discovery of these [1,3,4]thiadiazolo and [1,3,4]oxadiazolo[3,2-a]pyrimidin-5-one hybrids elicits their potentials as pursuable candidates for pancreatic cancer chemotherapy.
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U2 - 10.1016/j.bmcl.2020.127544
DO - 10.1016/j.bmcl.2020.127544
M3 - Article
C2 - 32920143
AN - SCOPUS:85090868454
SN - 0960-894X
VL - 30
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 22
M1 - 127544
ER -