STRUCTURE PRUNING TECHNIQUE PREPARED BY: S. MALATHI (M. PHARM) C. NAGENDRA PRASAD (M. PHARM) SIDDE. LAHARI (M. PHARM) P. ARAVINDA (M. PHARM) FROM: ASSISTANT PROFESSOR DEPARTMENT OF PHARMACEUTICAL ORGANIC CHEMISTRY KR COLLEGE OF PHARMACY BANGLORE.

STRUCTURE PRUNING Structure pruning is the refinement of the lead compound to improve the movement and diminish the undesirable impacts. At the end of the day, structure pruning means cutting of the structure and seeing its movement. This is one of the system for the streamlining of lead compound. Structure pruning is connected for a significant number of the mixes which results in improvement of the medication with the goal that it will be anything but difficult to blend the subordinates. It is a system much connected to the camptothecin and it was secluded from the bark and stem of Camptotheca acuminata. By the large camptothecin is having hostile to tumor action and have complex structure, however this method makes improvement of the camptothecin for simple amalgamation of its subordinates. Consequently the structure pruning method of camptothecin is given underneath.

ABOUT CAMPTOTHECIN CAMPTOTHECIN: Dynamic standard of alkaloid, one of the solid anticancer movement against to wide range of human malignancies. Progressively compelling for endless agony Have enormous number of reactions Subsequently, picked up enthusiasm for structure pruning.CHEMISTRY:  Molecular Formula ‎: C 20 H 16 N 2 O 4  IUPAC Name : 19-ethyl-19-hydroxy-17-oxa-3,13-diazapentacyclo[ ,11.0 4,9.0 15,20 ] henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione.  Common name : CAMPTOTHECIN

CAMPTOTHECIN - STRUCTURE PRUNING CPT has a planar quinoline pentacyclic alkaloid ring structure, that incorporates a pyrrolo[3,4-β]-quinoline moiety (rings A, B and C), conjugated pyridone moiety (ring D) and one chiral center at position 20 inside the alpha-hydroxy lactone ring with (S) configuration (the E-ring). Its planar structure is believed to be one of the most significant factors in topoisomerase restraint. 1) Ring-A: Benzene ring 2) Ring-B: Pyridine ring 3) Ring-C: Pyrrolidine 4) Ring-D: Pyridine-2-one 5) Ring-E: Lactone ring

CAMPTOTHECIN - STRUCTURE PRUNING REMOVAL RING E: OUT COME: Complete loss of activity. Analogue of camptothecin is increases the activity on topoisomerase I. CONCLUSION : The lactone ring is essential for activity, if we remove it complete loss of activity. Homocamptothecine is more potent than the parent molecule. Removing ring-E, double bonded O A B CD Change in ring size-E, A B CD E Homocamptothecine Inactive form

CAMPTOTHECIN - STRUCTURE PRUNING REMOVAL RING D: OUT COME: Complete loss of activity. CONCLUSION : The pyridinone ring is essential for activity, if we remove it complete loss of activity. In that basic Nitrogen is essential for anti-cancer activity. Removing ring-D, double bonded O, Inactive form A B C E

CAMPTOTHECIN - STRUCTURE PRUNING REMOVAL RING C: OUT COME: Complete loss of activity. CONCLUSION : The pyrrolidine ring is essential for anti-tumour activity, if we remove it complete loss of activity. In that basic Nitrogen is essential for anti-cancer activity. Removing ring - C, double bonded in ring B, A B E D Inactive form

CAMPTOTHECIN - STRUCTURE PRUNING REMOVAL RING B: OUT COME: Complete loss of activity. CONCLUSION : The pyrrolidine ring is essential for anti-tumour activity, if we remove it complete loss of activity. In that basic Nitrogen is essential for anti-cancer activity. Removing ring - B A C D E Inactive form

CAMPTOTHECIN - STRUCTURE PRUNING REMOVAL RING A: Camptothecin derivative OUT COME: Camptothecin derivative does not loss of activity. Substation on 9 TH position it leads to increases the topoisomerase to activity. Derivative is more potent then the parent molecule. CONCLUSION : The benzene ring is not essential for anti-tumour activity, if we remove it does not change on activity. Substituted derivatives is more potent because of electron withdrawn groups shows more activity. Removing ring - A B C D E Substitution on ring A at 9 TH position -N, -Cl, -Br B C D E A

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