title: Synthesis and biological evaluation of phaitanthrin congeners as anti-mycobacterial agents.
abstract: Natural alkaloid, tryptanthrin (indolo[2,1-b]quinazoline-6,12-dione) and its analogues are found to exhibit potent anti-tubercular activity against MDR-TB. A novel class of indolo[2,1-b]quinazolinones have been synthesized to evaluate their anti-mycobacterial activity. Enoyl-acyl carrier protein reductase (InhA) of Mycobacterium tuberculosis is one of the key enzymes and has been validated as an effective anti-microbial target. In silico molecular docking study demonstrates that the synthesized compounds exhibit high affinity for the M. tuberculosis drug target InhA. Phaitanthrin is a natural product, which belongs to a family of tryptanthrin and exhibits structural similarity except at position 6. Phaitanthrin derivatives are prepared by modifying the keto functionality of tryptanthrin. These phaitanthrin congeners are found to display promising anti-tubercular activity.
authors.affiliation: Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Hyderabad 500 037, India. Electronic address: ahmedkamal@iict.res.in.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Kamal
authors.affiliation: Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors.forename: B V Subba
authors.initials: BV
authors.lastname: Reddy
authors.affiliation: Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India; Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Hyderabad 500 037, India.
authors.forename: B
authors.initials: B
authors.lastname: Sridevi
authors.affiliation: Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Hyderabad 500 037, India.
authors.forename: A
authors.initials: A
authors.lastname: Ravikumar
authors.affiliation: Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors.forename: A
authors.initials: A
authors.lastname: Venkateswarlu
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Hyderabad 500 037, India.
authors.forename: G
authors.initials: G
authors.lastname: Sravanthi
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad 500078, India.
authors.forename: J Padma
authors.initials: JP
authors.lastname: Sridevi
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad 500078, India.
authors.forename: P
authors.initials: P
authors.lastname: Yogeeswari
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad 500078, India.
authors.forename: D
authors.initials: D
authors.lastname: Sriram
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D052999:Quinazolinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D052999:Quinazolinones; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)
keywords: Enoyl-acyl carrier protein reductase (InhA); In silico molecular docking study; Indolo[2,1-b]quinazoline-6,12-dione; MDR-TB; Tryptanthrin