BIOMAT Database Logo BIOMAT Database Logo

Synthesis and Biological Evaluation of Calothrixins B and their Deoxygenated Analogues. 2018

Bose Muthu Ramalingam, and Nachiappan Dhatchana Moorthy, and Somenath Roy Chowdhury, and Thiyagarajan Mageshwaran, and Elangovan Vellaichamy, and Sourav Saha, and Karthikeyan Ganesan, and B Navin Rajesh, and Saleem Iqbal, and Hemanta K Majumder, and Krishnasamy Gunasekaran, and Ramamoorthy Siva, and Arasambattu K Mohanakrishnan
Department of Organic Chemistry, University of Madras , Guindy Campus, Chennai 600 025, India.

A series of calothrixin B (2) analogues bearing substituents at the 'E' ring and their corresponding deoxygenated quinocarbazoles lacking quinone unit were synthesized. The cytotoxicities of calothrixins 1, 2, and 15b-p and quinocarbazole analogues were investigated against nine cancer cell lines. The quinocarbazoles 21a and 25a inhibited the catalytic activity of human topoisomerase II. The plasmid DNA cleavage abilities of calothrixins 1, 2, and 15b-p identified compound 15h causing DNA cleavage comparable to that of calothrixin A (1). Calothrixin A (1), 3-fluorocalothrixin 15h and 4-fluoroquinocarbazole 21b induced extensive DNA damage followed by apoptotic cell death. Spectral and plasmid unwinding studies demonstrated an intercalative mode of binding for quinocarbazoles. We identified two promising drug candidates, the 3-fluorocalothrixin B 15h with low toxicity in animal model and its deoxygenated derivative 4-fluoroquinocarbazole 21b as having potent cytotoxicity against NCI-H460 cell line with a GI50 of 1 nM.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D009690 Nucleic Acid Conformation The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape. DNA Conformation,RNA Conformation,Conformation, DNA,Conformation, Nucleic Acid,Conformation, RNA,Conformations, DNA,Conformations, Nucleic Acid,Conformations, RNA,DNA Conformations,Nucleic Acid Conformations,RNA Conformations
D010100 Oxygen An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration. Dioxygen,Oxygen-16,Oxygen 16
D002227 Carbazoles Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004250 DNA Topoisomerases, Type II DNA TOPOISOMERASES that catalyze ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. These enzymes bring about relaxation of the supercoiled DNA and resolution of a knotted circular DNA duplex. DNA Topoisomerase (ATP-Hydrolysing),DNA Topoisomerase II,DNA Topoisomerase II alpha,DNA Topoisomerase II beta,DNA Type 2 Topoisomerase,TOP2A Protein,TOP2B Protein,Topoisomerase II,Topoisomerase II alpha,Topoisomerase II beta,Type II DNA Topoisomerase,alpha, Topoisomerase II,beta, Topoisomerase II
D004353 Drug Evaluation, Preclinical Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications. Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular

Related Publications

Bose Muthu Ramalingam, and Nachiappan Dhatchana Moorthy, and Somenath Roy Chowdhury, and Thiyagarajan Mageshwaran, and Elangovan Vellaichamy, and Sourav Saha, and Karthikeyan Ganesan, and B Navin Rajesh, and Saleem Iqbal, and Hemanta K Majumder, and Krishnasamy Gunasekaran, and Ramamoorthy Siva, and Arasambattu K Mohanakrishnan
Cyanobacterial Metabolite Calothrixins: Recent Advances in Synthesis and Biological Evaluation.
January 2016, Marine drugs,
Bose Muthu Ramalingam, and Nachiappan Dhatchana Moorthy, and Somenath Roy Chowdhury, and Thiyagarajan Mageshwaran, and Elangovan Vellaichamy, and Sourav Saha, and Karthikeyan Ganesan, and B Navin Rajesh, and Saleem Iqbal, and Hemanta K Majumder, and Krishnasamy Gunasekaran, and Ramamoorthy Siva, and Arasambattu K Mohanakrishnan
Synthesis and biological evaluation of tamandarin B analogues.
February 2006, Organic letters,
Bose Muthu Ramalingam, and Nachiappan Dhatchana Moorthy, and Somenath Roy Chowdhury, and Thiyagarajan Mageshwaran, and Elangovan Vellaichamy, and Sourav Saha, and Karthikeyan Ganesan, and B Navin Rajesh, and Saleem Iqbal, and Hemanta K Majumder, and Krishnasamy Gunasekaran, and Ramamoorthy Siva, and Arasambattu K Mohanakrishnan
Total synthesis and biological evaluation of tamandarin B analogues.
July 2007, The Journal of organic chemistry,
Bose Muthu Ramalingam, and Nachiappan Dhatchana Moorthy, and Somenath Roy Chowdhury, and Thiyagarajan Mageshwaran, and Elangovan Vellaichamy, and Sourav Saha, and Karthikeyan Ganesan, and B Navin Rajesh, and Saleem Iqbal, and Hemanta K Majumder, and Krishnasamy Gunasekaran, and Ramamoorthy Siva, and Arasambattu K Mohanakrishnan
Synthesis and biological evaluation of B-ring analogues of (-)-rhazinilam.
April 2006, Bioorganic & medicinal chemistry,
Bose Muthu Ramalingam, and Nachiappan Dhatchana Moorthy, and Somenath Roy Chowdhury, and Thiyagarajan Mageshwaran, and Elangovan Vellaichamy, and Sourav Saha, and Karthikeyan Ganesan, and B Navin Rajesh, and Saleem Iqbal, and Hemanta K Majumder, and Krishnasamy Gunasekaran, and Ramamoorthy Siva, and Arasambattu K Mohanakrishnan
Concise total synthesis of calothrixins A and B.
July 2011, Organic letters,
Bose Muthu Ramalingam, and Nachiappan Dhatchana Moorthy, and Somenath Roy Chowdhury, and Thiyagarajan Mageshwaran, and Elangovan Vellaichamy, and Sourav Saha, and Karthikeyan Ganesan, and B Navin Rajesh, and Saleem Iqbal, and Hemanta K Majumder, and Krishnasamy Gunasekaran, and Ramamoorthy Siva, and Arasambattu K Mohanakrishnan
Anti-trypanosomatid benzofuroxans and deoxygenated analogues: synthesis using polymer-supported triphenylphosphine, biological evaluation and mechanism of action studies.
December 2009, European journal of medicinal chemistry,
Bose Muthu Ramalingam, and Nachiappan Dhatchana Moorthy, and Somenath Roy Chowdhury, and Thiyagarajan Mageshwaran, and Elangovan Vellaichamy, and Sourav Saha, and Karthikeyan Ganesan, and B Navin Rajesh, and Saleem Iqbal, and Hemanta K Majumder, and Krishnasamy Gunasekaran, and Ramamoorthy Siva, and Arasambattu K Mohanakrishnan
Design, synthesis, and biological evaluation of new territrem B analogues.
April 2005, Chemistry & biodiversity,
Bose Muthu Ramalingam, and Nachiappan Dhatchana Moorthy, and Somenath Roy Chowdhury, and Thiyagarajan Mageshwaran, and Elangovan Vellaichamy, and Sourav Saha, and Karthikeyan Ganesan, and B Navin Rajesh, and Saleem Iqbal, and Hemanta K Majumder, and Krishnasamy Gunasekaran, and Ramamoorthy Siva, and Arasambattu K Mohanakrishnan
Synthesis and antimalarial activity of calothrixins A and B, and their N-alkyl derivatives.
July 2012, Bioorganic & medicinal chemistry letters,
Bose Muthu Ramalingam, and Nachiappan Dhatchana Moorthy, and Somenath Roy Chowdhury, and Thiyagarajan Mageshwaran, and Elangovan Vellaichamy, and Sourav Saha, and Karthikeyan Ganesan, and B Navin Rajesh, and Saleem Iqbal, and Hemanta K Majumder, and Krishnasamy Gunasekaran, and Ramamoorthy Siva, and Arasambattu K Mohanakrishnan
Streamlined synthesis of phosphatidylinositol (PI), PI3P, PI3,5P2, and deoxygenated analogues as potential biological probes.
June 2006, The Journal of organic chemistry,
Bose Muthu Ramalingam, and Nachiappan Dhatchana Moorthy, and Somenath Roy Chowdhury, and Thiyagarajan Mageshwaran, and Elangovan Vellaichamy, and Sourav Saha, and Karthikeyan Ganesan, and B Navin Rajesh, and Saleem Iqbal, and Hemanta K Majumder, and Krishnasamy Gunasekaran, and Ramamoorthy Siva, and Arasambattu K Mohanakrishnan
Synthesis and biological evaluation of analogues of the antibiotic pantocin B.
October 2001, Journal of the American Chemical Society,
Copied contents to your clipboard!