PT  - JOURNAL ARTICLE
AU  - Thoukhir B. Shaik
AU  - M. Shaheer Malik
AU  - Zaki S. Seddigid
AU  - Sunitha R Routhu
AU  - Ahmed Kamal
TI  - Evaluation of anticancer and anti-mitotic properties of quinazoline and quinazolino-benzothiadiazine derivatives
AID  - 10.1101/108654
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 108654
4099  - http://biorxiv.org/content/early/2017/02/14/108654.short
4100  - http://biorxiv.org/content/early/2017/02/14/108654.full
AB  - Cancer is one of the major health and social-economic problems despite considerable progress in its early diagnosis and treatment. Owing to the emergence and increase of multi drug resistance to various conventional drugs, and the continuing importance on health-care expenditure, many researchers have focused to develop novel and effective anticancer compounds. In the present study, a series of in-house synthesized quinazoline and quinazolino-benzothiadiazine derivatives were investigated for their anticancer efficacy against a panel of five cancer (DU145, MCF7, HepG2, SKOV3 and MDA-MB-231) and one normal (MRC5) cell lines. Among all the tested compounds, fifteen of them exhibited promising growth-inhibitory effect (0.15 - 5.0 μM) and induced cell cycle arrest in G2/M phase. In addition, the selected compounds inhibited the microtubule assembly; altered mitochondrial membrane potential and enhanced the levels of caspase-9 in MCF-7 cells. Furthermore, the active compound with combination of drugs showed synergistic effect at lower concentrations and the drug uptake was mediated through clathrin mediated endocytic pathway. Our results indicated that quinazoline and quinazolino-benzothiadiazine conjugates could serve as potential leads in the development of personalized cancer therapeutics.Summary The present study describes the exploration of small molecules based on heterocyclic scaffolds for tubulin target based development of anticancer agents.