The United States on Friday added several senior Syrian officials including the ministers of oil and of finance and the leadership of a Russian bank to its sanctions blacklist.
"This widening of American sanctions against Russia ... at a time when the bloody attacks in Ankara and Berlin should bring reasonable people together to fight the terrorist threat shows that Washington has completely lost its grip on reality," the ministry said in a statement.
The US was trying to "'punish' us for our support to the Syrian government in the fight against terrorism which is a threat not only to that country but to the whole world", it said.
Washington's "desire for regime change in Syria is so strong that it is ready to help any destructive force", the ministry said.
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"We will not give in to sanctions," it said, adding that targeted Russian companies were "functioning normally".
Syria has been locked in war for more than five years, leaving more than 310,000 people dead and millions more displaced.
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The conflict began as a pro-democracy revolt but later morphed into an all-out civil war after President Bashar al-Assad's troops unleashed a brutal crackdown against dissent.
It has since become a complex, multi-front conflict, drawing in global powers as well as militias and jihadists.
While Western powers and some regional states have backed the rebellion, Russia and Iran have thrown their full weight behind Assad's regime.
In announcing the blacklist additions, Washington also imposed sanctions on Syrian airline Cham Wings, accused of transporting foreign militiamen to fight in the country's brutal civil war.
US officials also targeted two companies allegedly owned or operated by a Assad's cousin Rami Makhluf, which they said had handled oil drilled in areas controlled by the Islamic State group.
The east of Syria has fallen to IS and, while the regime and its allies have fought the extremists, officials have been accused of trading oil from jihadist-held territory.
The fresh sanctions came as the government recaptured the rebel-held east of Aleppo, the country's second city, after a fierce month-long offensive that saw thousands of civilians and rebels evacuated in recent days.
"The daily attacks on civilian centers by the government of Syria led by Bashar al-Assad are reprehensible, and both the Government and its enablers must be isolated and held accountable for their barbarism," said Adam Szubin, acting under secretary for terrorism and financial intelligence.
On Tuesday, the US Treasury had already announced new sanctions against Russia for its role in the Ukraine conflict, targeting Russian businessmen, bankers and transport companies.
