#GCG&GGS

[girishcalibration]

10 Best Tips to Choose the Right Weighing Scales

Looking for the perfect balance? 🤔 Discover our top 10 tips to select the ideal weighing scales for your needs! 🌟 From accuracy to design, we've got you covered. Dive in and tip the scales in your favor. 🔍⚖️

#WeighingScales #PrecisionBalance #TopTips #GCG&GGS #digitalscale

[postsofbabel]

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#posts of babel

[biomedicool]

Anti-cancer drugs - DNA targeting

Include alkylating agents, intercalating agents, and chain cutters.

Alkylating agents

Highly electrophilic species, looking for nucleophilic sites to attack, and forming covalent bonds to bases in DNA 

Prevent replication and transcription 

Toxic side effects (e.g. alkylation of proteins) 

Bind in the major groove of DNA

Both types cross-link DNA by covalently bonding to nitrogen of base pairs.

Binding of nucleic acid bases results in miscoding and distortion. 

Distortion of DNA prevents excision by HMG proteins – permanent damage. 

Transcription and replication prevented, tumour growth slows. 

Two electrophilic sites on an anticancer drug can cause interstrand and intrastrand cross-linking.

Preference for 1,2-GG or 1,2-GC linkage sites, with interstrand or intrastrand linkage, is dictated by drug chemical structure 

Other linkage adducts are possible. Eg 1,3-GCG, 1,2-GA. 

Monofunctional adducts are also possible 

Chlormethine (a nitrogen mustard)

 Chlormethine is highly reactive, toxic side effects. 

Lead compound for many less toxic mustard derivatives. 

Methyl (CH3 ) group has positive inductive effect – promotes loss of chloride – see mechanism 

Less toxic chlormethine analogues:

Melphalan:  e- withdrawing ring lowers Nu strength of N, less reactive drug, less side effects, less toxic. Mimics PhAla, carried into cells by transport proteins. 

Uracil mustard:  Uracil ring is e-withdrawing, less reactive alkylating agent. Mimics a nucleic acid base, concentrates in fast growing cells.

Cyclophosphamide:  Most commonly used alkylating agent, Non-toxic, orally active prodrug. Acrolein associated with toxicity.

Busulfan: Causes interstrand cross-linking. Sulphonate group withdraws electrons, adjacent carbon subject to Nu attack by DNA bases. 

Dacarbazine – A diazine:  Prodrug activated by oxidation in liver, decomposes to form methyldiazonium ion. Alkylates guanine groups 

INTERCALATING AGENTS

 Aminoacridines eg Proflavine

Antibiotics - Dactinomycin

Extra binding to sugar phosphate backbone by cyclic peptide 

Intercalates via minor groove of DNA double helix 

Prevents unwinding of DNA double helix 

Blocks transcription, blocks DNA-dependent RNA polymerase 

Anthracyclines eg Doxorubicin (adriamycin) 

 Extra binding to sugar phosphate backbone by NH3 Planar rings and Anthracyclines eg Doxorubicin (adriamycin) 

Intercalates via major groove of DNA double helix 

 A topoisomerase poison - blocks action of topoisomerase II by stabilising DNA-enzyme complex 

CHAIN CUTTERS 

Calicheamicin g1 I antitumour agent 

 Nucleophilic attack on trisulphide chain starts a rearrangement process. 

This interacts with DNA to generate a DNA diradical, which reacts with oxygen, resulting in chain cutting.

Bleomycins (BLM)

Highly active head, neck, testicular cancer (Hodgkin lymphoma) 

Single and double-strand cleavage of DNA with several reduced metal ions and O2 , Fe(II) highest in vivo activity. 

Three regions - 

bithiazole DNA binding domain (DBD) locks BLM into the minor groove, 

carbohydrate domain (CHD) H-bonds BLM to sugar phosphate of DNA 

metal binding domain (MBD) bonds to Fe(II)    

Mechanism

A reaction with hydrogen peroxide gives Fe(III) and hydroxyl radicals which abstract H atoms and cut the DNA chain. 

Fe2+ + H2O2 Fe3+ + OH. + OH− Fenton mechanism 

Lungs and skin have low levels of BLM hydrolase - higher sensitivity and toxicity. Pneumonitis occurs in about 10% of patients, progresses to pulmonary fibrosis. Over-expressed in malignant cells, resistance to bleomycin    

Summary of Anti-Tumour Specificity for DNA 

Major groove alkylators 

GG interstrand - N-mustards, nitrosoureas. 

GG intrastrand - methanesulphonates. 

GC-interstrand - nitrosoureas, triazines. 

Minor groove intercalators 

GG interstrand – anthracyclines. 

GC-interstrand – actinomycins, acridines. 

Minor groove chain cutters 

GC or GT intrastrand – bleomycins 

#cancer #chemotherapy #dna #notes #pharmacology #biomedicine #biology #biochemistry #human biology #cancer therapy #studyblr #medblr #science #2 #3

[masrourbarzani]

Masrour Barzani   مه‌سرور بارزانی و فالح فه‌یاز له‌ میونشن كۆبوونه‌وه‌  

مه‌سرور بارزانی، راوێژكاری ئه‌نجوومه‌نی ئاسایشی هه‌رێمی كوردستان، له‌ په‌راوێزی كۆنگره‌ی ئاسایشی میونشن له‌ ئه‌ڵمانیا، له‌گه‌ڵ فالح فه‌یاز، راوێژكاری ده‌زگای ئاسایشی نیشتمانی عێراق كۆبووه‌وه‌.

به‌ گوێره‌ی زانیارییه‌كان، له‌ كۆبوونه‌وه‌كه‌دا، گفتوگۆ له‌ باره‌ی گرنگی دیاریكردنی میكانیزمێك بۆ هه‌ماهه‌نگی نێوان پێشمه‌رگه‌ و هێزه‌ عێراقییه‌كان كرایه‌وه‌ بۆ ناوچه‌ كوردستانییه‌كانی ده‌ره‌وه‌ی ئیداره‌ی هه‌رێمی كوردستان (ناوچه‌ جێناكۆكه‌كان).

مه‌سرور بارزانی روونیشی كرده‌وه‌، كرده‌وه‌كانی چه‌كدارانی رێكخراوی داعش له‌ پارێزگاكانی كه‌ركووك، نه‌ینه‌وا، سه‌ڵاحه‌ددین و دیاله‌ و چه‌ند ناوچه‌یه‌كی ئه‌نبار زیادیان كردووه‌ته‌وه‌.

راوێژكاری ئه‌نجوومه‌نی ئاسایشی هه‌رێمی كوردستان، دووپاتی له‌وه‌ش كردووه‌ته‌وه‌، به‌ره‌نگاربوونه‌وه‌ی داعش و فكری توندڕه‌وی رێكخراوه‌كه‌، پێویستی به‌ هه‌ماهه‌نگی نێوان حكوومه‌تی هه‌رێمی كوردستان و حكوومه‌تی فیدرالی هه‌یه‌.

له‌ باره‌ی ئاسایی كردنه‌وه‌ی ره‌وشی كه‌ركووكیش، هه‌ردوولا كۆك بوون له‌سه‌ر ئاساییكردنه‌وه‌ی دۆخی كه‌ركووك به‌ گوێره‌ی مادده‌ی 140ی ده‌ستووری هه‌میشه‌یی عێراق.

هه‌ر له‌ كۆبوونه‌وه‌كه‌دا، ره‌وشی سووریا و بارودۆخی ناوچه‌كه‌ به‌ گشتی تاووتوێ كرا.