Copper mediated decarboxylative direct C-H arylation of heteroarenes with benzoic acids

Decarboxylative coupling reactions to date require a stoichiometric oxidant (such as copper and silver salts) for decarboxylation purposes along with a metal catalyst (e.g. palladium) for cross-coupling. In this communication, an economic and sustainable approach by using a simple copper salt was developed in the presence of molecular oxygen as the sole oxidant. A wide range of 5-membered heteroarenes undergo aryl–heteroaryl cross-coupling with electron deficient aryl carboxylic acids

Deregulation of LIMD1-VHL-HIF-1α-VEGF pathway is associated with different stages of cervical cancer.

To understand the mechanism of cellular stress in basal-parabasal layers of normal cervical epithelium and during different stages of cervical carcinoma, we analyzed the alterations (expression/methylation/copy number variation/mutation) of HIF-1α and its associated genes LIMD1, VHL and VEGF in disease-free normal cervix (n = 9), adjacent normal cervix of tumors (n = 70), cervical intraepithelial neoplasia (CIN; n = 32), cancer of uterine cervix (CACX; n = 174) samples and two CACX cell lines. In basal-parabasal layers of normal cervical epithelium, LIMD1 showed high protein expression, while low protein expression of VHL was concordant with high expression of HIF-1α and VEGF irrespective of HPV-16 (human papillomavirus 16) infection. This was in concordance with the low promoter methylation of LIMD1 and high in VHL in the basal-parabasal layers of normal cervix. LIMD1 expression was significantly reduced while VHL expression was unchanged during different stages of cervical carcinoma. This was in concordance with their frequent methylation during different stages of this tumor. In different stages of cervical carcinoma, the expression pattern of HIF-1α and VEGF was high as seen in basal-parabasal layers and inversely correlated with the expression of LIMD1 and VHL. This was validated by demethylation experiments using 5-aza-2'-deoxycytidine in CACX cell lines. Additional deletion of LIMD1 and VHL in CIN/CACX provided an additional growth advantage during cervical carcinogenesis through reduced expression of genes and associated with poor prognosis of patients. Our data showed that overexpression of HIF-1α and its target gene VEGF in the basal-parabasal layers of normal cervix was due to frequent inactivation of VHL by its promoter methylation. This profile was maintained during different stages of cervical carcinoma with additional methylation/deletion of VHL and LIMD1.This work was supported by CSIR (Council of Scientific and Industrial Research, Government of India)-JRF/NET grant [File No.09/030(0059)/2010-EMR-I] to Mr. C.Chakraborty, grant [Sr. No. 2121130723] from UGC (University Grants Commission, Government of India) to Mr. Sudip Samadder, grant [SR/SO/HS-116/2007] from DST (Department of Science and Technology, Government of India) to Dr. C. K. Panda and grant [ No. 60(0111)/14/EMR-II of dt.03/11/2014] from CSIR (Council of Scientific and Industrial Research, Government of India) to Dr. C. K. Pand

Acrocyanosis: An overview

Introduction: It is a functional peripheral vascular disorder characterized by bluish discoloration of skin and mucous membrane due to diminished oxyhemoglobin. It may be due to central or local tissue oxygenation defects. It is a painful episodic disorder, where trophic changes and ulceration are very rare except in necrotizing variant. By definition, it refers to persistent abnormally deep blue or cyanotic discoloration of skin over extremities (hand and feet most commonly) due to decreased oxyhemoglobin. Etiology: It can be both primary and secondary to psychiatric, neurologic, autoimmune, infective, metabolic and other causes. The existing hypothesis suggests the prevailing role of vasospastic reaction over possible blood rheology impairment. [1] As per the current line of thinking, it is due to chronic vasospasm of small cutaneous arteries, and arterioles along with compensatory dilatation in the capillary and post capillary venules causes cyanosis and sweating. Clinical Features: Acrocyanosis is an uncommon condition. It usually presents with coolness and violaceous dusky discolorations of hands and less frequently the feet. Other peripheral part like ear, nose, lips and nipple can also be affected. [2] The changes may be transient after cold exposure but frequently persist during winter and even in summer. Management: There is no standard and curative medical or surgical treatment of acrocyanosis. In mild cases, it is unnecessary to give any drug treatment. Life style modification, dietary and hygiene counseling, avoidance of cold and reassurance that the bluish skin discoloration does not indicate any serious illness is all that is necessary

Photosensitized Nickel Catalysis Enabled Silyl Radical Mediated Direct Activation of Carbamoyl Chlorides to Access (Hetero)aryl Carbamides

The transformation of a readily available molecule to a medicinally relevant functionality is the heart of organic synthesis which literally unfolds new direction in the field of drug discovery and development. Accordingly, synthetic chemistry fraternity is constantly striving to introduce a range of avant-garde techniques to construct an incredibly important fundamental entity like “amide bonds” which connect the amino acids in proteins and exist as a prevalent structural motif in biomolecules. In this context, we want to introduce the concept of cross-electrophile coupling by merging the photoredox and transition metal catalysis to construct carbamides from superabundant (hetero)aryl chlorides or bromides along with commercially feasible carbamoyl chlorides. However, there is barely any report on direct activation of carbamoyl chloride so far. To circumvent the challenge, we employ the intrinsic affinity of silyl radical species towards halogen atom to harness the carbamoyl radical directly from carbamoyl chlorides which is seemingly the first of its kind. The success of this protocol relies on the prior formation of ‘aryl halides to Ni-catalyst’ oxidative addition intermediate that assists in generation of the vital carbamoyl radical. The breadth of application of this technique is significantly demonstrated by the synthesis of a plethora of (hetero)aryl carbamides with diverse functionalities. As stated earlier, we outline the direct utility of this protocol by the late-stage amidation of halide containing drug molecules and pharmacophores

Marjolin ulcer with multifocal origin

Marjolin ulcer developed from a twenty years old post burn scar. The patient presented with chronic ulceration followed by multifocal development of squamous cell carcinoma with different growth pattern. One nodular lesion grew rapidly to produce a large lesion with history of a little bleeding after trauma but without any pain. Excision followed by skin grafting resulted in good cosmetic scar

Remittent idiopathic necrotizing acrocyanosis - A rare entity

Remittent idiopathic necrotizing acrocyanosis is a very rare condition characterized by persistent systemic cyanotic or erythrocyanotic discoloration of hands and feet. It is associated with pain, tenderness of fingers and toes and may present as ulceration or gangrene of extremities. It is aggravated with cold exposure but persists even in summer. Acrocyanosis is not due to any systemic disease; peripheral arteriolar constriction with secondary vasodilatation due to disordered vascular tone of unknown etiology has been postulated. It responds to peripheral vasodilator drug but usually needs continuous long term therapy along with avoidance of cold exposure. We report the case of a 53-year-old male farmer with remittent necrotizing acrocyanosis

REMITTENT IDIOPATHIC NECROTIZING ACROCYANOSIS - A RARE ENTITY

Remittent idiopathic necrotizing acrocyanosis is a very rare condition characterized by persistent systemic cyanotic or erythrocyanotic discoloration of hands and feet. It is associated with pain, tenderness of fingers and toes and may present as ulceration or gangrene of extremities. It is aggravated with cold exposure but persists even in summer. Acrocyanosis is not due to any systemic disease; peripheral arteriolar constriction with secondary vasodilatation due to disordered vascular tone of unknown etiology has been postulated. It responds to peripheral vasodilator drug but usually needs continuous long term therapy along with avoidance of cold exposure. We report the case of a 53-year-old male farmer with remittent necrotizing acrocyanosis