title: Novel substituted hydrazono indolo[2,1-b]quinazoline-6,12-dione analogues as cytostatic agents: Synthesis, crystal structure, biological evaluation and molecular docking studies.
abstract: A series of novel substituted hydrazono indolo[2,1-b]quinazoline-6,12-dione analogues have been synthesized and screened for their in vitro cytotoxic and antimicrobial activities. Among all the target compounds, 3c exhibited the most potent inhibitory activity against three cancer cell lines MCF-7, A549, HeLa with IC50values 07.14±1.285μM, 09.18±0.968μM and 10.57±0.581μM respectively, while maintaining low toxicity towards non-cancer originated cell line, HEK-293. The detailed studies about molecular interactions with probable target protein indoleamine 2,3-dioxygenase (IDO1) were done by using docking simulations. The results from docking models are in consistent with the experimental in vitro cytotoxic activity conclusions i.e. 3c shows the highest binding energy -11.25kcal/mol. Furthermore, antimicrobial studies revealed that the compound 3e has shown excellent anti bacterial activity against four tested strains and the compounds 3b, 3e and 3f have shown good anti fungal activity against two tested organisms as compared with their standard drugs.
authors: Department of Chemistry, Kakatiya University, Warangal 506009, India.
authors: Ramu
authors: R
authors: Guda
authors: Department of Chemistry, Kakatiya University, Warangal 506009, India.
authors: Sirassu
authors: S
authors: Narsimha
authors: School of Chemistry, University of Hyderabad, Hyderabad 500046, India.
authors: Ramavath
authors: R
authors: Babu
authors: University College of Pharmaceutical Sciences, Kakatiya University, Warangal 506009, India.
authors: Srujana
authors: S
authors: Muthadi
authors: University College of Pharmaceutical Sciences, Kakatiya University, Warangal 506009, India.
authors: Harikiran
authors: H
authors: Lingabathula
authors: Department of Chemistry, Kakatiya University, Warangal 506009, India.
authors: Rambabu
authors: R
authors: Palabindela
authors: University College of Pharmaceutical Sciences, Kakatiya University, Warangal 506009, India.
authors: Narsimha Reddy
authors: NR
authors: Yellu
authors: Department of Chemistry, Panjab University, Chandigarh 160014, India. Electronic address: girijeshchem@gmail.com.
authors: Girijesh
authors: G
authors: Kumar
authors: Department of Chemistry, Kakatiya University, Warangal 506009, India. Electronic address: mamathakasula2016@gmail.com.
authors: Mamatha
authors: M
authors: Kasula
mesh_terms: D000072283:A549 Cells; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy; D005658:Fungi / Q000187:drug effects; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D061986:MCF-7 Cells; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D009181:Mycoses / Q000188:drug therapy; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D006835:Hydrazones; C576710:IDO1 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D011799:Quinazolines; C046243:tryptanthrine
keywords: Antibacterial activity; Antifungal activity; Cytotoxicity; IDO1; Molecular docking; Tryptanthrin